Bone marrow transplantation with T-cell-depleted grafts: II. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted bone marrow grafts disparate at minor histocompatibility antigens

Graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (BMT), can be prevented by in vitro depletion of T cells from the bone marrow (BM) prior to transplantation. The purpose of this study was to assess the role of BM T cells in the reconstitution of various immune functions following BMT across minor histocompatibility barriers. Lethally irradiated CBA/J (H-2^k) mice were grafted with either 10⁷ unseparated or T-cell-depleted BM cells from Β10.BR (H-2^k, minor-histoincompatible) mice. Blood counts, BM colonies in agar, and various immune functions of spleen cells from the recipient mice were tested 2—12 weeks post-BMT and compared with those of normal donors. The following observations were made: (A) Peripheral blood lymphocyte counts decreased to 30% of normal 2 weeks post-BMT with almost normal recovery at 8 weeks. (B) The percentage of Thyl.2+ splenocytes reached normal levels at 8 weeks post-BMT. (C) The number of BM colonies (GM-CFU) was reduced to 10% at 2 weeks and fully recovered at 12 weeks. (D) Proliferative response to the B-cell mitogen LPS was fully reconstituted after 4 weeks; however, anti-SRBC PFC (following Mishell-Dutton cultures) was restored 50% at 8-12 weeks. (E) Reconstitution of T cell functions including proliferative responses to concanavalin A, phytohemagglutinin, and allogeneic leukocytes, and allocytotoxicity, did not exceed 50% even 12 weeks post-BMT. Overall, depletion of T cells from donor BM allografts incompatible at minor histocompatibility loci, did not seem to significantly alter the rate of immunohematopoietic reconstitution in the lethally irradiated BM recipients.