Expansion of regulatory CD8 + CD25 + T cells after neonatal alloimmunization

Summary Transplantation tolerance induced by neonatal injection of semi‐allogeneic spleen cells is associated with a pathological syndrome caused by T helper type 2 (Th2) differentiation of donor‐specific CD4 + T lymphocytes. We have shown previously that this Th2‐biased response is inhibited by host CD8 + T cells. Herein, we demonstrate that upon neonatal immunization with (A/J × BALB/c)F 1 spleen cells, BALB/c mice expand a population of CD8 + T cells expressing both CD25 and forkhead box P3 (FoxP3) markers. In this setting, CD8 + CD25 + T cells predominantly produce interferon (IFN)‐γ and interleukin (IL)‐10 and are efficient in controlling IL‐4, IL‐5 and IL‐13 production by donor‐specific CD4 + T cells in vitro . CD8 + FoxP3 ‐ T cells are single producers of IFN‐γ or IL‐10, whereas CD8 + FoxP3 + T cells are double producers of IFN‐γ and IL‐10. We further demonstrate that IFN‐γ and IL‐10 are two major cytokines produced by CD8 + T cells involved in the in vivo regulation of Th2‐type pathology. In this setting, we conclude that neonatal alloimmunization induces the expansion of several regulatory CD8 + T cells which may control Th2 activities via IFN‐γ and IL‐10.