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

ABSTRACT

OBJECTIVE: Immunization 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 METHODS: T-lymphocyte responses were analyzed in vivo by depletion and transfer experiments and ex vivo by proliferation assay and cytokine measurements. RESULTS: Mouse 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. CONCLUSIONS: Our 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.