are memory t cells cd4 or cd8

Memory T cells may be either CD4 + or CD8 + and usually express CD45RO and at the same time lack CD45RA. [16] Central memory T cells (T CM cells) express CD45RO, C-C chemokine receptor type 7 (CCR7), and L-selectin (CD62L). Central memory T cells also have intermediate to high expression of CD44.

Full Answer

Is CD4 and T4 the same thing?

Is CD4 and T4 the same thing? CD4, also known as T4, is a 55 kD single-chain type I transmembrane glycoprotein expressed on most thymocytes, a subset of T cells, and monocytes/macrophages. CD4, a member of the Ig superfamily, recognizes antigens associated with MHC class II molecules, and participates in cell-cell interactions,

What is the difference between CD3 and CD4 cells?

CD3 Absolute Count. The number of all T cells, which includes CD4 and CD8 cells. This figure is rarely used for making treatment decisions. CD3 Percentage. The proportion of all immune cells that are T cells. This figure is also rarely used for making treatment decisions. CD4 Cell Count. The absolute number of CD4 cells.

How many CD4 T cells do we have?

The level of CD4+ T-lymphocytes is known as the CD4 cell count or just the CD4 count. It is an indication of the strength of the body’s immune defenses. A normal CD4 count is between 500 to 1500 cells per cubic millimeter (mm3). It is sometimes designated as a percentage.

What does CD4 T cell mean?

CD4 T-cells are T-lymphocytes that have molecules called CD4 on their surface. They start the immune response by signaling other defensive immune cells to infectious pathogens such as bacteria and viruses. CD8 T-cells which have molecules on their surface called CD8.

Are memory T cells CD8?

CD8 T cells of memory phenotype and function can arise in response to self-peptide and/or in a lymphopenic environment in response to cytokines that trigger homeostatic proliferation (“virtual” and “innate” memory) (35, 36).

Are memory T cells CD4?

Memory CD4 T cells are classically defined as the set of T cells produced during a primary immunogenic challenge that persist and are capable of generating a recall response to secondary challenge.

What is the memory T cell?

However, a small portion of long-lived T cells still remains for rapid response upon pathogen re-exposure. This kind of cells is called memory T cells. Because memory T cells have been trained to recognize specific antigens, they will trigger a faster and stronger immune response after encountering the same antigen.

Are T helper cells memory cells?

These cells serve to 'remember' the specific antigen involved in this encounter, so that should this antigen enter the body again the T helper cells would be able to activate B cells much faster. Subsequently, antigen-specific antibodies are produced.

Do cytotoxic T-cells produce memory cells?

The control of the differentiation pathways followed by responding CD8(+) T cells to produce protective memory cells has been intensely studied. Recent developments have identified heterogeneity at the effector cytotoxic T-lymphocyte level within which a bona fide memory cell precursor has emerged.

How do memory cells differ from effector cells?

Specifically, memory cells have a higher degree of sialylation on 1 O-glycans and express lower levels of 2 O-glycans than effector cells;33–36 this difference can be detected using an antibody that binds specifically to CD43 only when this molecule has been modified by 2 O-glycans.

Which cells are memory cells?

B lymphocytes are the cells of the immune system that make antibodies to invading pathogens like viruses. They form memory cells that remember the same pathogen for faster antibody production in future infections.

Where are memory T cells made?

Memory T cells are established at both lymphoid and peripheral sites following the clearance of an invading pathogen.

What is not required for the generation of CD8 memory T cells?

These studies established that virus-specific memory CD8+ T cells do not require antigen or MHC for their maintenance, but rely on IL-15 for homeostasis and IL-7 for survival, whereas memory CD4+ T cells require TCR signalling and/or MHC class II molecules for their functional maintenance and homeostasis127–129.

What is CD4+ T cells responsible for?

A type of lymphocyte. CD4 T lymphocytes (CD4 cells) help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells), to fight infection.

What are CD4 and CD8 cells?

CD4 cells are also called T-helper cells, T-suppressor cells, and cytotoxic T-cells. They help the body fight infections. CD8 cells are also called cytotoxic T-lymphocytes. They help fight cancer and germs that live inside your cells (intracellular pathogens).

Do memory CTL require T helper cells?

Various experiments and observations have demonstrated that CD4 T cells are not required for the long-term maintenance of memory B cells/and or antibody release by plasma cells. There is clear evidence that humoral immunity steadily persists for many years while CD4 T cell memory declines [75, 76, 79].

Are memory cells B cells?

In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades.

Do memory CTL require T helper cells?

Various experiments and observations have demonstrated that CD4 T cells are not required for the long-term maintenance of memory B cells/and or antibody release by plasma cells. There is clear evidence that humoral immunity steadily persists for many years while CD4 T cell memory declines [75, 76, 79].

What is the difference between central memory T cells and effector memory T cells?

One possibility is that effector memory cells present an immediate, but not sustained, defense at pathogen sites of entry, whereas central memory T cells sustain the response by proliferating in the secondary lymphoid organs and producing a supply of new effectors (21–23).

Do memory cells produce antibodies?

Memory B cells are generated during primary responses to T-dependent vaccines. They do not produce antibodies, i.e., do not protect, unless re-exposure to antigen drives their differentiation into antibody producing plasma cells.

What is a memory T cell?

Memory T cell. Subset of T lymphocytes that might have some of the same functions as memory B cells. For other uses, see Memory cell (disambiguation). Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear.

What is the function of memory T cells?

Primary function of memory cells is augmented immune response after reactivation of those cells by reintroduction of relevant pathogen into the body. It is important to note that this field is intensively studied and some information may not be available as of yet.

Which T cells have CD44?

Central memory T cells also have intermediate to high expression of CD44. This memory subpopulation is commonly found in the lymph nodes and in the peripheral circulation. Effector memory T cells (T EM cells) express CD45RO but lack expression of CCR7 and L-selectin. They also have intermediate to high expression of CD44.

What happens to a naive T cell after it encounters an antigen?

1. After the naive T cell (N) encounters an antigen it becomes activated and begins to proliferate ( divide) into many clones or daughter cells.

Why do T cells react to antigens?

It is found that memory T cells can sometimes react to novel antigens, potentially caused by intrinsic diversity and breadth of the T cell receptor binding targets. These T cells could cross-react to environmental or resident antigens in our bodies (like bacteria in our gut) and proliferate.

How do memory T cells maintain their function?

Currently, the mechanism behind memory T cell maintenance is not fully understood. Activation through T cell receptor may play a role. It is found that memory T cells can sometimes react to novel antigens, potentially caused by intrinsic diversity and breadth of the T cell receptor binding targets. These T cells could cross-react to environmental or resident antigens in our bodies ( like bacteria in our gut) and proliferate . These events would help maintain the memory T cell population. The cross-reactivity mechanism may be important for memory T cells at the mucosal tissues since these sites have higher antigen density. For those resident in blood, bone marrow, lymphoid tissues and spleen, homeostatic cytokines (including IL-17 and IL-15) or major histocompatibility complex II (MHCII) signaling may be more important.

Why are T CM lymphocytes important?

T CM : T CM lymphocytes have several attributes in common with stem cells, the most important being the ability of self-renewal, mainly because of high level of phosphorylation on key transcription factor , STAT5. In mice, T CM proved to confer more powerful immunity against viruses, bacteria and cancer cells, compared to T EM lymphocytes in several experimental models.

How long do CD4 and CD8 memory cells last?

When the stability of CD4 + and CD8 + memory cells was directly compared, mice infected with LCMV were found to have CD8 + memory responses that were sustained at a steady state for 3 years, whereas memory CD4 + T cells gradually decreased over this 3-year period 22. This is the clearest evidence that, during a viral infection, there is a demonstrable difference in the longevity of CD4 + and CD8 + memory cells. The considerable stability noted for memory CD8 + T cell responses after viral infection in naive mice needs to be considered in a more physiologic context in which multiple exposures to different viral infections occur over a lifetime in the host. Exposure to heterologous viral infections substantially diminished the frequency of CD8 + T cells from a previous viral infection 74. Finally, when the frequency of virus-specific CD4 + and CD8 + T cells after heterologous viral infections or protein antigen immunizations was compared, again there was reduction of memory CD8 + T cells but not CD4 + T cells specific to viruses from earlier infections 75. Thus, although CD4 + and CD8 + memory pools seem to be regulated independently, the history of prior antigenic exposure and homeostatic mechanisms may serve to regulate the magnitude of memory CD8 + responses.

What is required to sustain CD4 memory T cells?

What is required to sustain CD4 + and CD8 + memory T cells has been reviewed 70. For CD4 + and CD8 + memory cells, antigen and MHC class I or II are not essential for survival. For CD8 + memory T cells, IL-7 and IL-15 are important in regulating T cell survival and turnover, respectively. CD4 + memory T cells do not require expression of the common cytokine receptor γ chain for survival, providing indirect evidence that cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15 may not be required for the maintenance of CD4 + memory cells 71; however, IL-7 may indeed be important in sustaining the survival of memory CD4 + T cells 72. With regard to costimulatory molecules, there is evidence that OX-40 and OX-40 ligand may be involved in sustaining CD4 + T cell survival 73.

What happens to the effector T cells during apoptosis?

CD8 + effector cells that survive apoptosis during this contraction phase develop into durable long-term resting memory cells 22. The initial 'burst size' of the CD8 + effector T cell response correlates with the magnitude of the long-term memory response 66. However, the larger primary burst size seen with CD8 + T cells in response to viral infections is associated with a more profound decay than is noted for CD4 + T cells, probably reflecting a homeostatic mechanism to maintain a certain number of CD8 + memory cells 67. As discussed above, CD4 + IFN-γ-producing cells do not efficiently develop into resting memory cells, although activated CD4 + T cells stimulated in T H 1-polarizing conditions that have not yet become IFN-γ-producing cells (T H 1-lineage cells or uncommitted) are able to develop into long-term memory cells. For T H 2 cells, a heterogeneous population of activated CD4 + T cells cultured in T H 2 conditions develops into resting memory cells 68. These observations indicate that CD4 + IFN-γ + cells differ from CD8 + effector T cells in their transition to resting memory cells.

What factors affect the frequency of CD4+ and CD8+ effector T cells?

Thus, several factors, such as the type of pathogen, the nature of the infection (acute versus chronic) and the cells presenting antigen, will regulate the frequency of CD4 + and CD8 + effector T cells.

What is the most accurate method to determine antigen specific T cells?

The development of techniques to analyze responses at the single-cell level, such as MHC tetramers, enzyme-linked immunospot analysis and intracellular cytokine staining, has allowed more accurate quantification of antigen-specific T cells. Because of the much greater availability of reagents such as MHC class I tetramers and well defined immunodominant epitopes for viral infections, the preponderance of data comparing frequencies of CD4 + and CD8 + effector cytokine producing cells has been generated in mouse models of viral infection. The frequency of virus-specific CD8 + IFN-γ-producing cells is substantially higher than that for CD4 + IFN-γ-producing cells both at the peak and throughout the memory response in mice infected with LCMV 22, Sendai 23 or vaccinia 24. Similarly, in human Epstein-Barr virus infection, the clonal expansion of Epstein-Barr virus–specific CD8 + T cells is greater than that for CD4 + T cells 25. Comparable data were also obtained in mouse models of infection with L. monocytogenes 19. These notable differences in the magnitude of CD4 + and CD8 + T cell responses to such infections could be due to many factors. First, because the intrinsic proliferative capacity of CD8 + T cells seems to be greater than that of CD4 + T cells, a small change in the number of cell divisions would have a substantial effect on the number of effector cells at the end of the response. For LCMV infection, it was estimated that CD4 + T cells underwent approximately 9 cell divisions, compared with 15 divisions for CD8 + T cells, during the first week after infection 22. Similarly, for listeria infection, there was also a difference in cell division between CD4 + and CD8 + T cells, resulting in higher numbers of listeria-specific CD8 + T cells 19. Another reason for the higher CD8 + responses may be that the efficiency of antigen presentation is better for CD8 + than for CD4 + T cells. This difference in antigen presentation efficiency could be because fewer cells express MHC class II compared with MHC class I. In addition, viral infections, through their normal endogenous processing, or listeria infection, through listeriolysin O, would allow for very efficient MHC class I antigen presentation. A third consideration for the better CD8 + responses is that cytokines such as IL-2 and IL-15 may have a more profound effect in sustaining the proliferative capacity of CD8 + T cells than for CD4 + T cells early in the course of activation 8. Finally, regulatory mechanisms mediated by cytotoxic T lymphocyte antigen 4 (CTLA-4) or increased susceptibility to apoptosis could have a greater effect in limiting the expansion and promoting the death of CD4 + effector T cell responses 26.

How do naive T cells differentiate?

Naive CD4 + T cells have multiple potential pathways for differentiating from naive to effector and then to memory cells. For T H 1 cells, because CD4 + IFN-γ-producing effector cells are relatively short-lived in vivo and do not efficiently develop into memory cells, differentiation is likely to follow a progressive and linear pathway. CD4 + IL-4-producing T cells may have multiple potential pathways of memory cell differentiation. CD8 + T cells readily develop into effector cells after activation. After the contraction phase of the response, CD8 + T cells seem to proceed to effector T EM and then T CM cells. T EM and T CM cells have comparable cytolytic and cytokine-producing capacity, but the T CM population has enhanced proliferative capacity.

What are T helper type 1 and T helper type 2?

After being activated, naive CD4 + T cells differentiate into functional subsets called T helper type 1 (T H 1) and T helper type 2 (T H 2) cells, based on their production of cytokine interferon (IFN)-γ and interleukin (IL)-4, respectively 1. T H 1 cells are essential for protection against a variety of intracellular infections, whereas T H 2 responses can be protective against certain extracellular infections. CD8 + T cells mediate their effector functions through production of cytokines such as IFN-γ and tumor necrosis factor (TNF)-α and/or by cytolytic mechanisms. Such responses are important in preventing or maintaining control against disease in a variety of intracellular infections and perhaps also against certain tumors. This review discusses the similarities and differences in the mechanisms regulating the generation and maintenance of CD4 + and CD8 + effector and memory T cells.

Why is it important to understand the signals that regulate the development of memory T cells?

Understanding the signals that regulate the development of memory T cells is crucial to efforts to design vaccines capable of eliciting T cell-based immunity. CD4 + T cells are essential in the formation of protective memory CD8 + T cells following infection or immunization.

How do T cells respond to cancer?

Similar to chronic infection, the immune response to cancer is marked by the persistence of antigen that can lead to a loss of T cell function 117. Accordingly, CD4 + T cell help can promote, whereas T Reg cells suppress, the antitumour CD8 + T cell response 118, 119, 120, 121. CD4 + T cells can enhance the recruitment, proliferation and effector function of CD8 + T cells within the tumour 121, 122. The secretion of IFNγ induces the expression of chemokines that are necessary to recruit CD8 + T cells to the tumour, whereas the production of IL-2 by tumour-specific CD4 + T cells can promote CD8 + T cell proliferation and expression of granzyme B 121. CD4 + T cells can also directly suppress tumour growth through IFNγ and cytotoxic functions 123. Conversely, T Reg cells within the tumour can interact with DCs and suppress the expression of CD80 and CD86, leading to the induction of a dysfunctional state within CD8 + T cells that is marked by high expression of inhibitory receptors and poor effector function 119. Given that T cell effector functions are highly dependent on glucose and glutamine, T cell-nutrient deprivation by T Reg cells may be another component of immunosuppression observed in the tumour microenvironment 124, 125, 126. Currently, many therapies are aimed at delivering CD4 + T cell help to tumour sites, including vaccinations and adoptive T cell transfer 127, 128, 129. It is important to learn how CD4 + T cells are involved in the durable responses observed in some patients following immunotherapy treatment.

What is the resolution phase of T cells?

During the resolution phase, as the levels of type I IFNs wane, there is an expansion of activated T Reg cell populations. IL-10 secretion by activated T Reg cells can suppress the maturation state of DCs and limit their secretion of pro-inflammatory cytokines, thus allowing the preservation of less-differentiated effector CD8 + T cells 49. T Reg cell expression of CTLA4 acts in a similar manner by limiting CD80 and/or CD86 stimulation on DCs by CD28 (Ref. 50 ). Effector CD8 + T cells are then able to continue to mature and develop into memory CD8 + T cells that can rapidly respond on pathogen re-encounter. T Reg cells also act during the resolution phase to modulate TGFβ levels within mucosal tissues, thereby bolstering the induction of CD8 + T RM cells 94. Following the resolution phase, CD4 + T cells may contribute to the maintenance of memory CD8 + T cells through suppression of the outgrowth of viral reservoirs that could drive terminal exhaustion of CD8 + T cells.

What is the function of T-reg cells?

In addition to this function, T Reg cells can act during the priming phase to suppress the magnitude of the CD8 + T cell response, thereby restricting the number of cells that survive into the memory phase 81, 82, 83. However, type I IFNs generated early after viral infection can directly inhibit T Reg cell activation and proliferation, facilitating the generation of a robust effector T cell response 84. As the levels of type I IFNs wane, T Reg cell expansion occurs; the newly populating T Reg cells display an activated phenotype with more robust IL-10 expression relative to T Reg cells present in the steady state 49, 85 ( Box 2 ). IL-10-competent T Reg cells are mainly located in the white pulp of the spleen, near to DCs as well as memory precursor CD8 + T cells, which is an optimal position to suppress the activation state of DCs and thus protect CD8 + T cells from excess bystander inflammation and preserve their state as memory precursors 49, 73, 86, 87, 88.

What is the role of T-reg cells in the CNS?

T Reg cells also may have a role in the formation of CD8 + T RM cells. In the absence of T Reg cells, reduced numbers of CD8 + T RM cells were retained in the central nervous system (CNS) following infection with West Nile virus. The reduction in T RM cell numbers is associated with decreased amounts of TGFβ in the CNS, suggesting that T Reg cell-dependent modulation of TGFβ levels may be important in driving CD8 + T RM cell formation and retention in mucosal tissues 94 ( Fig. 3c ). This finding further supports a new, perhaps paradoxical, role for T Reg cells in providing helper functions as opposed to suppressive functions for the generation of long-term T cell immunity.

What is the role of regulatory T cells in infection?

Regulatory T (T Reg) cells act during the resolution phase of infection to protect CD8 + T cells from inflammatory signals and promote the survival of a CD8 + T cell pool capable of robustly expanding upon secondary infection.

What are T-regulatory T cells?

CD4 + regulatory T (T Reg) cells express the transcription factor forkhead box P3 (FOXP3) and are crucial for the prevention of excess immunopathology or autoimmunity through many mechanisms 126. T Reg cells have considerable functional and phenotypic heterogeneity. Central or naive T Reg cells express CD62L and are predominantly found in the circulation and secondary lymphoid tissues. Following exposure to antigen and/or interleukin-2 (IL-2), T Reg cells adopt a more effector-like state and downregulate CD62L expression and progressively upregulate expression of CD69 and killer cell lectin-like receptor subfamily G, member 1 (KLRG1). Acquisition of a more effector-like phenotype is accompanied by enhanced expression of suppressive molecules, such as IL-10 and cytotoxic T lymphocyte antigen 4 (CTLA4), and KLRG1 + T Reg cells represent a terminally differentiated population 49, 85.

How do CD8 T cells differ from CD4 T cells?

Similar to our previous studies we saw that CD8 T cells expanded in both lymphoid and peripheral organs whereas CD4 T cells did not significantly expand in numbers in either lymphoid or peripheral organs because in addition to proliferating, they also were undergoing apoptosis. Interestingly, we noticed that among CD8 T cells, while the expansions were comparable across organs, we noted that the phenotypes of these expanded cells varied in the peripheral organs compared to the lymphoid, as peripheral organs had elevated NKG2D, PD-1, and KLRG1. In contrast, CD4 T cell phenotypes were relatively consistent across all organs. We show that the composition of the memory/activated (CD44 high) at a given site weighs heavily on the activation marker expression at that site with those being more rich in the effector/effector memory T cell subsets having elevated expression of activation markers across the board. Importantly, PBMC samples from patients receiving systemic high dose IL-2 therapy express elevated levels of PD-1 on the T E/EM subset as well. In summary, these data highlight the critical need to assess immune phenotype and function not only in lymphoid organs, but direct sites of inflammation in order to get an accurate picture of what is occurring locally. Furthermore, it suggests the systemic effector/effector memory population may directly correlate with the phenotype of the cells at peripheral sites.

What is the function of memory CD8 T cells?

Under these conditions, memory CD8 T cells can be activated purely by exposure to elevated cytokines causing them to expand and upregulate markers such as NKG2D which can confer the ability to respond to target cells that are inappropriately expressing stress ligands instead of through recognition of cognate antigen in the context of MHC, consistent with alternative bystander activation. Importantly, we have shown that these bystander activated memory CD8 T cells do not upregulate markers consistent with TCR engagement, namely CD25 and PD-1. In contrast, CD4 T cells activated under the same conditions undergo proliferation which is heavily coupled with apoptosis resulting in a net insignificant expansion of this cell type. This apoptosis was shown to be IFNg dependent [ 7] and thought to be occurring through differential expression of PD-1 on CD4 T cells following cytokine-induced, antigen-independent stimulation [ 8 ]. While we have exhaustively characterized these opposing roles in both CD4 and CD8 T cells following systemic immunotherapy, the majority of our conclusions have been drawn from data derived from secondary lymphoid organs (i.e., spleen and lymph nodes) and not in the periphery such as the tumor or metastatic sites.

What are the phenotypes of CD4 and CD8 T cells?

In mice, CD4 and CD8 T cells can be further categorized into memory and naïve phenotypes based on CD62L (L-selectin) and CD44 expression with the CD44 low CD62L+ population considered naïve (T N ), CD44 high CD62L+ population considered central memory (T CM ), and the CD44 high CD62L neg population considered effector and/or effector memory (T E/EM ). It is known that CD4 and CD8 T cells differ in their distribution of these subsets in lymphoid and peripheral organs. While naïve frequencies within CD4 and CD8 populations remain relatively similar, the CD44 high population is more central memory skewed in CD8 T cells and effector memory skewed in CD4 T cells in a resting organism [ 12, 13 ]. However, in the peripheral organs, tissue resident T cells within both the CD4 and CD8 T cell subsets are predominantly of the effector memory phenotype [ 14 ].

What organs are T cells in?

Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype.

Do CD4 and CD8 T cells have PD-1?

In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to CD62L low (T effector/effector memory,T E/EM) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on T E/EM cells was observed in patients undergoing systemic high-dose IL-2 therapy.

Does immunotherapy affect memory?

We and others have previously shown that strong immunostimulatory therapies for cancer induce potent proliferation of memory (CD44 high) CD4 and CD8 T cells in the spleen and lymph nodes [ 6 ]. It was also observed that CD4, but not CD8, T cells also undergo activation induced cell death in an interferon (IFN)-γ dependent fashion resulting in insignificant overall expansion of CD4 T cells by numbers in these same organs compared to baseline [ 7 ]. These data were generated using lymphoid organ readouts. However, in light of phenotypes observed in the MIN-O bearing, immunotherapy treated mice, the expansion, activation, and apoptosis of activated T cells may be differentially affected in the peripheral tissues. Therefore, we sought to further characterize and compare T cell activation in peripheral organs (where the primary tumor and/or metastatic lesions may reside) and secondary lymphoid organs (which are often surveyed during immunotherapeutic studies to assess mechanisms of action). We evaluated CD8 and CD4 T cell (Foxp3 neg) frequency, expansion, and apoptosis systemically in both lymphoid and peripheral organs. Consistent with previous reports by our group, while not significantly altering their overall frequency (Fig. 1a ), anti-CD40/IL-2 immunotherapy resulted in significant expansion in total numbers of CD8 T cells in the spleens and lymph nodes (Fig. 1b ). In line with increases in total CD8 numbers, the frequency of CD8 T cells that incorporated bromodeoxyuridine (BrdU) in vivo was significantly expanded and the proportion of apoptotic cells as assessed by extracellular Annexin V expression was not significantly different from controls (Fig C-D). In contrast, total CD4 T cell frequency decreased and numbers did not change significantly compared to controls within the same organs (Fig. 1a-b ). While CD4 T cells were expanding as assessed by BrdU incorporation, a significant proportion of them were going through apoptosis as well (Fig. 1c-d) resulting in a net insignificant change in total numbers. These data were in line with what was previously observed [ 7 ]. When we assessed non-lymphoid organs including lungs and liver, we saw similar trends in both CD4 and CD8 T cells, namely that CD8 T cells were expanding and surviving across all organs following IT (Fig. 2a-b) whereas CD4 T cells (Foxp3 neg) were expanding and concurrently going through apoptosis to a similar extent resulting in insignificant changes to both their frequencies and numbers (Fig. 2c-d) in the periphery.

Does IL-2 help with tumor growth?

Combination of anti-CD40 with IL-2 has been shown to induce delayed growth and regression across several murine tumor models [ 6, 7, 10 ]. Similar to published data using cell line tumor models, treatment of the mammary intraepithelial neoplasia-outgrowth (MIN-O) model [ 9 ], a tissue transplant line, with anti-CD40 and IL-2 immunotherapy (IT) led to significant anti-tumor responses ( P = 0.0057) including regression in >50% of the treated mice (Additional file 1: Figure S1A). Previous studies have shown these anti-tumor responses to be due to CD8 T cells therefore we assessed T cell phenotype in the spleen as well as within the tumor and lungs (a common metastatic site for many different tumor models). While we noted therapy generally induced CD8 expansion across all organs, we noted some differences in CD8 T cell memory phenotype across organ sites (Additional file 1: Figure S1B-C).

Overview

Sub-populations

Historically, memory T cells were thought to belong to either the effector (TEM cells) or central memory (TCM cells) subtypes, each with their own distinguishing set of cell surface markers (see below). Subsequently, numerous additional populations of memory T cells were discovered including tissue-resident memory T (TRM) cells, stem memory TSCM cells, and virtual memory T cells. The single unifying theme for all memory T cell subtypes is that they are long-lived and ca…

Function

Lineage debate

Epigenetic modifications

TCR-independent (bystander) activation