A Role for CD40 Expression on CD8
            <sup>+</sup>
            T Cells in the Generation of CD8
            <sup>+</sup>
            T Cell Memory

Bourgeois, Christine; Rocha, Bénédita; Tanchot, Corinne

doi:10.1126/science.1072615

Cited by 579 publications

(584 citation statements)

References 23 publications

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“…CD8 cells, engaged in the presence or absence of CD4 cell help, occur in similar frequencies after the primary immune response, but differ fundamentally in terms of functionality. The former represent memory cells that can exert effector functions, while the latter are "lethargic cells" that undergo apoptosis after antigen reencounter and do not mediate immunity [6][7][8]. Functional T cells occur in different effector classes, such as Th1, Th2, and beyond [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

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It is unknown to what extent the heterogeneity of antigen presenting cells (APC) influences the IFN-γ response of CD4 memory cells. We restimulated DO11.10 T cell receptor (TCR)-transgenic cells and wild-type CD4 memory cells with OVA-peptide 323 -339 presented on purified dendritic cells (DC), macrophages, and B cells. Using IFN-γ ELISPOT assays we measured the number of cytokine producing T cells and the amount of cytokine produced by individual T cells at different time points after antigen encounter. The data showed that, when CD4 cells recognized antigen on DC, the induction of cytokine production was accelerated compared to macrophages and B cells. In contrast, the per-cell cytokine productivity was independent of the type of APC by which the T cells were restimulated. Moreover, the peptide concentration required for CD4 cell activation was comparable for the different APC. The data suggest that DC induce cytokine production in memory cells with accelerated activation kinetics, whereas 24 h of antigen stimulation on DC, macrophages, and B cells results in comparable levels of T cell activation. These data have implications for the understanding of T cell memory responses when T cells re-encounter antigen on different APC as well as for the monitoring of memory T cell responses ex vivo.

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Section: Introductionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

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“…Furthermore, helper T lymphocytes have been found to be important for the development of T-cell memory. 24,26,27 Without help supplied by CD4 + T cells, T-cell memory generation can be severely hampered, as reflected by both decreased proliferation and diminished capacity to exert effector functions. Immune responses against leukemic cells might therefore also be more efficient when both T-cell subsets functionally contribute.…”

Section: Introductionmentioning

confidence: 99%

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

et al. 2005

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Both cytotoxic T cells and helper T cells are important in immune responses against pathogens and malignant cells.In hematological malignancies which express HLA class II molecules, immunotherapy may be directed to HLA class II restricted antigens. We investigated whether it is possible to engineer HLA class II restricted T cells with both antigenspecific cytolytic activity and the capacity to produce high amounts of cytokines. CD4 + and CD8 + peripheral-bloodderived T cells were retrovirally transduced with the HLA class II restricted minor histocompatibility antigen dead box RNA helicase Y (DBY)-specific TCR. The TCR-transduced CD4 + T cells exerted DBY-specific cytolytic activity, produced Th0, Th1, or Th2 cytokines, and proliferated upon DBY-specific stimulation. TCR-transduced CD8 + T cells exerted cytolytic activity which equaled the level of cytolytic activity of the TCR-transferred CD4 + T cells. Cotransfer of CD4 enhanced the cytolytic activity of the TCR-transduced CD8 + T cells, but introduction of CD4 was not sufficient to generate DBY-specific CD8 + T cells with the capacity to produce high amounts of cytokines. In this study, we demonstrated the feasibility to engineer T cells with antigen-specific cytolytic activity, as well as the ability to produce significant amounts of cytokines, by TCR transfer to CD4 + T cells. Gene Therapy (2005) IntroductionPatients relapsing from leukemia after allogeneic stem cell transplantation can successfully be treated by donor lymphocyte infusions (DLI), due to the graft-versusleukemia (GVL) response of the donor-derived T cells. [1][2][3][4] However, DLI is also associated with graft-versus-hostdisease (GVHD). Several studies have illustrated that depletion of CD8 + T cells from the DLI may preserve the beneficial GVL reactivity without the induction of GVHD, indicating that the CD4 + T lymphocytes may play an essential role in the antileukemic reactivity. [5][6][7][8][9][10] The mechanism by which the CD4 + T cells contribute to the GVL response is, however, not known. CD4 + T cells have been suggested to elicit the antileukemic response via the induction of minor histocompatibility antigen (mHag)-specific CD8 + T cells. 5 In addition, mHag-specific CD4 + T-helper cells have been reported to mature dendritic cells and enhance the expansion of mHag-specific cytotoxic T lymphocytes in vitro. 11 Alternatively, we have demonstrated that CD4 + T cells are capable of exerting direct cytolytic activity against leukemic cells. [12][13][14] Cellular immunotherapeutic approaches based on the adoptive transfer of T lymphocytes may require large cell numbers. Large numbers of T cells with a defined antigen specificity can be acquired by retroviral transfer of the T-cell receptor to peripheral-blood-derived T lymphocytes. Until now, the application of retroviral transfer of TCRs has mainly been limited to the transfer of HLA class I restricted TCRs. [15][16][17][18][19][20] However, the specificity of HLA class II restricted T lymphocytes can also be transferred to other T c...

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“…First, CD4 + T cells expressing CD40L activate APC through CD40 and these "licensed" APC are then able to drive CD8 + T cell responses [9][10][11]. Secondly, CD4 + T cells expressing CD40L may directly deliver help to CD8 + T cells [7]. Besides the CD40-CD40L interaction, other receptor-ligand interactions such as the CD27-CD70 interaction may be important for generating functional CD8 + memory T cells [12].…”

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confidence: 99%

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

2008

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CD4 + T cell help during the priming of CD8 + T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8 + T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4 + T cells instruct CD8 + memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27 high whereas memory CTL primed in the absence of CD4 + T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27 -/-memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4 + T cells control CTL memory.Key words: CD27 Á CD4 T cell help Á Costimulation Á LCMV Á T cell memory IntroductionAfter an acute infection, the initial expansion of CTL is determined by a brief period of antigenic stimulation followed by a contraction to a stable pool of long-lived memory cells [1][2][3]. Memory CTL are characterized by an increased frequency of specific CD8 + T cells with a heightened sensitivity to an antigen that has been encountered previously. The cellular basis influencing memory CTL formation has been the focus of extensive research. Several studies highlighted the importance of CD4 + T cells in the generation of CTL memory [4][5][6]. Memory T lymphocytes that are primed in the absence of CD4 + T cell help have a reduced proliferation capacity. In addition, the production of acute effector cytokines and IL-2 are reduced [7]. "Unhelped" CD8 + T cells die upon in vitro re-activation, due to the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is not expressed by "helped" CD8 + memory T cells [8].The mechanisms how CD4 + T cell help drives CD8 + T cell memory has not been resolved in detail. Mice deficient for CD40L have CD8 + memory T cells with reduced function. The CD40-CD40L interaction may be involved in the generation of CTL memory via two mechanisms. First, CD4 + T cells expressing CD40L activate APC through CD40 and these "licensed" APC are then able to drive CD8 + T cell responses [9][10][11]. Secondly, CD4 + T cells expressing CD40L may directly deliver help to CD8 + T cells [7]. Besides the CD40-CD40L interaction, other receptor-ligand interactions such as the CD27-CD70 interaction may be important for generating functional CD8 + memory T cells [12]. In addition, soluble signals may be involved in CD8 + T cell formation. It has been reported that IL-4-secreting CD4 + T cells are involved in the formation of memo...

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A Role for CD40 Expression on CD8 ⁺ T Cells in the Generation of CD8 ⁺ T Cell Memory

Cited by 579 publications

References 23 publications

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

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A Role for CD40 Expression on CD8 + T Cells in the Generation of CD8 + T Cell Memory

Cited by 579 publications

References 23 publications

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

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A Role for CD40 Expression on CD8 ⁺ T Cells in the Generation of CD8 ⁺ T Cell Memory

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression