Direct CD4 Help Provision following Interaction of Memory CD4 and CD8 T Cells with Distinct Antigen-Presenting Dendritic Cells

Herve, Marie-Ghislaine de Goër de; Dembelé, Bamory; Vallée, Mélissa; Herr, Florence; Cariou, Anne; Taoufik, Yassine

doi:10.4049/jimmunol.0904209

Cited by 19 publications

(22 citation statements)

References 43 publications

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“…3a). This period of activation with DCs in the presence of CD4 T cells was necessary for secondary expansion of resting memory CD8 T cells and for their differentiation into cytotoxic secondary effectors821. As shown in Fig.…”

Section: Resultsmentioning

confidence: 92%

FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory

et al. 2012

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During the primary immune response, CD8 memory emerges from an environment of strong immune activation. The FoxP3+ regulatory CD4 T-cell subset (Treg) is known as a key suppressive component of the immune system. Here we report that Tregs are required for the generation of functional CD8 memory. In the absence of Tregs during priming, the resulting memory cells proliferate poorly and fail to differentiate into functional cytotoxic secondary effectors following antigen reactivation. We find that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors. This crucial new role of Tregs has implications for optimal vaccine development.

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Section: Resultsmentioning

confidence: 92%

FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory

et al. 2012

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“…If communication between CD4 T cells and other cells, including DC, B cells, CD8 T cells and macrophages, operates preferentially at relatively short range [54]–[59] then variable expression of cytokines by individual T cells may also increase the variability of the phenotypes of these other effector cells. For example, IL-2 drives CD8 cells toward a memory cell phenotype, whereas IFNγ induces the CD8 cells to become effector cells [60].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Diversity in the Th1-Dominated Human Anti-Influenza Response Caused by Variable Cytokine Expression by Th1 Cells, and a Minor Population of Uncommitted IL-2+IFNγ- Thpp Cells

2014

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Within overall Th1-like human memory T cell responses, individual T cells may express only some of the characteristic Th1 cytokines when reactivated. In the Th1-oriented memory response to influenza, we have tested the contributions of two potential mechanisms for this diversity: variable expression of cytokines by a uniform population during activation, or different stable subsets that consistently expressed subsets of the Th1 cytokine pattern. To test for short-term variability, in vitro-stimulated influenza-specific human memory CD4+ T cells were sorted according to IL-2 and IFNγ expression, cultured briefly in vitro, and cytokine patterns measured after restimulation. Cells that were initially IFNγ+ and either IL-2+ or IL-2- converged rapidly, containing similar proportions of IL-2-IFNγ+ and IL-2+IFNγ+ cells after culture and restimulation. Both phenotypes expressed Tbet, and similar patterns of mRNA. Thus variability of IL-2 expression in IFNγ+ cells appeared to be regulated more by short-term variability than by stable differentiated subsets. In contrast, heterogeneous expression of IFNγ in IL-2+ influenza-specific T cells appeared to be due partly to stable T cell subsets. After sorting, culture and restimulation, influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ cells maintained significantly biased ratios of IFNγ+ and IFNγ- cells. IL-2+IFNγ- cells included both Tbetlo and Tbethi cells, and showed more mRNA expression differences with either of the IFNγ+ populations. To test whether IL-2+IFNγ-Tbetlo cells were Thpp cells (primed but uncommitted memory cells, predominant in responses to protein vaccines), influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ T cells were sorted and cultured in Th1- or Th2-generating conditions. Both cell types yielded IFNγ-secreting cells in Th1 conditions, but only IL-2+IFNγ- cells were able to differentiate into IL-4-producing cells. Thus expression of IL-2 in the anti-influenza response may be regulated mainly by short term variability, whereas different T cell subsets, Th1 and Thpp, may contribute to variability in IFNγ expression.

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“…In contrast, agonistic anti-CD40 and anti-4-1BBL mAbs and peptide-pulsed DCs could not overcome the diabetes resistance of 17 T cell memory against viral (7,8,10), bacterial (9), and self-Ags (11) in the absence of CD4 + cells is defective, resulting in reduced survival of memory CD8 + cells and impaired responsiveness to secondary antigenic challenge. The CD4 + Th cell signals responsible for promoting autoregulatory CD8 + T cell memory formation remain unclear, but might be similar to those involved in effector T cell memory formation (24)(25)(26)(27). It has also been suggested that unhelped memory CD8 + T cells tend to commit suicide by secreting TRAIL in response to a secondary antigenic challenge (28).…”

Section: Discussionmentioning

confidence: 99%

Development of Memory-Like Autoregulatory CD8+ T Cells Is CD4+ T Cell Dependent

Shameli

Clemente-Casares²,

Wang³

et al. 2011

The Journal of Immunology

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Progression of spontaneous autoimmune diabetes is associated with development of a disease-countering negative-feedback regulatory loop that involves differentiation of low-avidity autoreactive CD8+ cells into memory-like autoregulatory T cells. Such T cells blunt diabetes progression by suppressing the presentation of both cognate and noncognate Ags to pathogenic high-avidity autoreactive CD8+ T cells in the pancreas-draining lymph nodes. In this study, we show that development of autoregulatory CD8+ T cell memory is CD4+ T cell dependent. Transgenic (TG) NOD mice expressing a low-affinity autoreactive TCR were completely resistant to autoimmune diabetes, even after systemic treatment of the mice with agonistic anti-CD40 or anti–4-1BB mAbs or autoantigen-pulsed dendritic cells, strategies that dramatically accelerate diabetes development in TG NOD mice expressing a higher affinity TCR for the same autoantigenic specificity. Furthermore, whereas abrogation of RAG-2 expression, hence endogenous CD4+ T cell and B cell development, decelerated disease progression in high-affinity TCR-TG NOD mice, it converted the low-affinity TCR into a pathogenic one. In agreement with these data, polyclonal CD4+ T cells from prediabetic NOD mice promoted disease in high-affinity TCR-TG NOD.Rag2−/− mice, but inhibited it in low-affinity TCR-TG NOD.Rag2−/− mice. Thus, in chronic autoimmune responses, CD4+ Th cells contribute to both promoting and suppressing pathogenic autoimmunity.

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Direct CD4 Help Provision following Interaction of Memory CD4 and CD8 T Cells with Distinct Antigen-Presenting Dendritic Cells

Cited by 19 publications

References 43 publications

FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory

FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory

Cytokine Diversity in the Th1-Dominated Human Anti-Influenza Response Caused by Variable Cytokine Expression by Th1 Cells, and a Minor Population of Uncommitted IL-2+IFNγ- Thpp Cells

Development of Memory-Like Autoregulatory CD8+ T Cells Is CD4+ T Cell Dependent

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