Title: DONOR T CELLS ARE NOT REQUIRED FOR INDUCTION OF ALLOGRAFT TOLERANCE IN MICE TREATED WITH ANTILYMPHOCYTE SERUM, RAPAMYCIN, AND DONOR BONE MARROW CELLS1
Abstract: Background. Postgraft infusion of donor bone marrow cells (BMC) effectively induces tolerance to skin allografts in antilymphocyte serum- and rapamycin-treated recipients in fully major histocompatibility complex-mismatched mouse strain combinations.We used various gene knockout mice to examine the role of donor T cells and B cells in BMC-induced allograft tolerance. Methods. All recipient mice received ALS on days −1 and 2 and rapamycin (6 mg/kg) on day 7 relative to fully major histocompatibility complex-mismatched skin grafting on day 0. Donor BMC prepared either from mice lacking CD4- and/or CD8a-, or CD3ε-expressing cells or B cells, or from corresponding wild-type mice, were given on day 7. The level and phenotypes of chimerism was determined by flow cytometry. Results. All T cell- and B cell-deficient BMC were as effective as wild-type BMC in inducing prolongation of skin graft survival. A low degree of chimerism without donor type T cells was detected in tolerant mice given T cell-deficient BMC or wild-type BMC 60 days after transplantation. Chimeric cells were composed of B cells and macrophages/monocytes. Low level chimerism without donor T or B cells was also present in tolerant mice given B cell-deficient BMC. Conclusion. Donor type T cells and T cell chimerism are not required for induction of allograft tolerance by the antilymphocyte serum /rapamycin/donor BMC-infusion protocol. Donor B cells also do not participate in tolerance induction. Thus, infusion of T cell-depleted BMC in conjunction with conventional immunosuppressive regimens will be a simple, safe, and effective way to induce allograft tolerance in clinical organ transplantation.