Alteration of Molecules and Cytokines Related to the Activation of T Lymphocyte in Immune Tolerance Induced Mice Model / 대한이식학회지

ABSTRACT

PURPOSE: Monoclonal antibodies (mAb) specific for CD45RB as a potent tolerogenic target can prolong allograft survival in several animal models. The mechanisms of CD45RB mAb-mediated tolerance are largely unknown. Therefore, the present studies were performed to determine the immunomodulatory effects of CD45RB mAb on T cells in early or late time after allogenic skin transplantation. METHODS: Skin grafts and bone marrows from BALB/c donor mice were transplanted on C57BL/6 recipient mice and Busulfan was administerd. Group 1 was composed of anti-CD154 mAb administerd mice, group 2 was composed of anti-CD154 and anti-CD45RBB mAb administerd mice, and group 3 consisted of anti-CD154 mAb and CTLA4-Ig administerd mice. The proportion of splenic CD4+ and CD8+ T cell and range of CD45RB was observed by flow cytometry. Cytokines secreted by CD4+ T cell were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: CD45RB mAb in combination with CD154 mAb enhanced graft survival in allogenic skin transplantation model where CD45RB mAb specific for CD45RB, which was proven mainly expressed by CD8+ T cells, had inhibitory effects on the proportion of splenocyte-derived CD8+ and CD4+CD45RB(high) T cells in early or late time posttransplant. CONCLUSION: The combined therapy showed decreases in the proliferation of CD8+ T cells in vivo and allospecific responses of IFN-gamma-producing cells. Such immunomodulatory effects may be associated with the tolerogenic ability of CD45RB mAb in allogenic skin transplantation.