CD8+ T-cell-mediated killing of donor dendritic cells prevents alloreactive T helper type-2 responses in vivo. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Blood Année : 2006

CD8+ T-cell-mediated killing of donor dendritic cells prevents alloreactive T helper type-2 responses in vivo.

Résumé

Accumulating evidence indicates that, in absence of CD8+ T-cell activation, CD4+ T-cell-mediated allograft rejection is associated with a dominant Th2-cell response and eosinophil infiltrates. In this study, we analyzed the mechanisms by which CD8+ T cells regulate alloreactive CD4+ T-cell priming and differentiation into interleukin 4 (IL-4)-producing cells. We showed that interferon gamma (IFN-gamma) production by CD8+ T cells was dispensable for the inhibition of Th2-cell development, as well as tissue eosinophilia and type 2 cytokine production in the rejected grafts. Since we noticed that CD8+ T cells not only suppressed Th2 differentiation, but also down-modulated the overall priming of alloreactive CD4+ T cells, we evaluated whether CD8+ T cells act by limiting the accumulation of donor-derived dendritic cells (DCs) in lymph nodes. We found that indeed, alloreactive CD8+ T cells rapidly eliminated allogeneic DCs from T-cell areas of draining lymph nodes, through a perforin-dependent mechanism. Thus, our data demonstrate that cytotoxic T lymphocyte (CTL)-mediated clearance of allogeneic DCs is a negative feedback mechanism that limits the duration of alloantigen presentation in draining lymph nodes, thereby modulating the amplitude and polarization of the primary alloreactive CD4+ T-cell responses.

Domaines

Immunologie

Dates et versions

hal-00458864 , version 1 (22-02-2010)

Identifiants

Citer

Sophie Laffont, Jérôme D Coudert, Lucile Garidou, Laurent Delpy, Aurélie Wiedemann, et al.. CD8+ T-cell-mediated killing of donor dendritic cells prevents alloreactive T helper type-2 responses in vivo.. Blood, 2006, 108 (7), pp.2257-64. ⟨10.1182/blood-2005-10-4059⟩. ⟨hal-00458864⟩
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