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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 spleen cells, BALB/c mice expand a population of CD8 T cells expressing both CD25 and forkhead box P3 (FoxP3) markers. In this setting, CD8CD25 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. CD8FoxP3 T cells are single producers of IFN-γ or IL-10, whereas CD8FoxP3 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. [ABSTRACT FROM AUTHOR]

BALB/c mice made tolerant to A/J alloantigens by neonatal injection of (A/J × BALB/c)F1 spleen cells develop a host-versus-graft (HVG) disease due to the activation of donor B cells by a subset of host alloreactive helper T cells. We have investigated the effects of a single neonatal injection of the 145-2C11 anti-mouse CD3 monoclonal antibody (MoAb) on the establishment of allotolerance and on the development of the immunopathological features of HVG disease. First, this treatment did not modify the specific anti-donor cytotoxic T lymphocyte (CTL) unresponsiveness or the persistence of circulating immunoglobulins bearing donor allotype. Second, the hyper IgE, the hyper IgG 1 and the increased expression of Ia antigens on B cells found in untreated HVG mice were not observed after injection of the 145-2C11 MoAb. Likewise, treated mice displayed lower levels of anti-DNA IgG antibodies and less glomerular immune deposits as compared with untreated HVG mice. We conclude that the administration of the anti-CD3 MoAb did not interfere with the induction of allotolerance but exerts a pronounced inhibitory effect on the associated immunopathological syndrome. [ABSTRACT FROM AUTHOR]