Characterization of the T-lymphocyte response elicited by mouse immunization with rat platelets

ObjectiveImmunization of normal CBA mice with rat platelets leads to an autoantibody response directed against mouse platelets. The purpose of this work was to determine the involvement of T lymphocytes in this response.Materials and MethodsT-lymphocyte responses were analyzed in vivo by depletion and transfer experiments and ex vivo by proliferation assay and cytokine measurements.ResultsMouse immunization with rat platelets induced production of antibodies reacting with rat and mouse platelets. This response was found to depend on CD4+ T-helper lymphocytes reacting with rat, but not with mouse platelets. These anti-rat platelet T-helper cells were mainly of the Th1 phenotype. When transferred into naïve mice, they enhanced the anti-mouse platelet antibody response induced by subsequent immunization with rat platelets. In addition, depletion of CD25+ cells enhanced the thrombocytopenia induced by immunization with rat platelets, whereas adoptive transfer of CD4+CD25+ cells from immunized mice suppressed it.ConclusionsOur results suggest that activation of anti-rat platelet T-helper cells can bypass the mechanism of tolerance and result in the secretion of autoreactive antibodies, but this response is still controlled by regulatory T cells that develop progressively after immunization.