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

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)F₁ 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.