Immunization with donor splenocytes in testis of recipient mice promotes induction of long-term survival of islet allografts transplanted in a conventional site (TRAN1P.920)

Abstract

Immune responses are subdued in immune privileged sites, which provide a unique opportunity to prolong cellular allograft survival. We and others have previously shown that inducing tolerance of islet allografts transplanted in murine testes is easier than in conventional sites. However, it is not practical to transplant islets in human testes. Here we found that immunization of B6 recipients with irradiated Balb/C splenocytes through testicular injection, 7 and 14 days before islet transplantation under the kidney capsule, promotes long-term allograft survival induced by low doses of anti-CD40L (MR1) or CTLA4-Ig (0.1mg/day, days 0,2,4,6), with 75% islet allografts achieving long-term survival (>120 days). Same Ab treatment without the immunization failed to do so. Immunization without MR1 or CTLA4-Ig did not prolong allograft survival. We also found that islet transplantation under renal capsule of previously immunized recipients generates much less CD44+CD8+ memory T cells but induces more CD4+CD25+ Tregs than under renal capsule of unimmunized recipients. These Tregs exhibited donor-specific suppression of alloimmune responses in vitro. These findings reveal new mechanisms of immune privilege and may provide novel approaches to inducing long-term allograft survival or transplant tolerance in both immunologically privileged and unprivileged sites.