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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 γ (IFN-γ) 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.