Influence of graft versus host reaction on the T cell repertoire differentiating from bone marrow precursors following allogeneic bone marrow transplantation

Abstract

When lethally irradiated AKR (Mls-1a) mice were reconstituted with bone marrow (BM) cells plus a small number (0.5%) of mature T cells from allogeneic B10.AQR or B10 (Mls-1b) mice and minor GVHR was induced in the recipients, almost complete donor chimerism was accomplished in the early stages after reconstitution. By contrast, in irradiated AKR mice reconstituted with T cell-depleted BM cells alone from B10 or B10.AQR mice, radio-resistant T cells of recipient origin persisted for a relatively long period in peripheral lymphoid tissues. In this paper the influence of residual T cells in the chimeric mice on generation of the T cell repertoire derived from donor BM is discussed. It will be demonstrated that the recipient (AKR) T cells are capable of producing Mls-1a antigens (Ag) after lethal irradiation in vivo. These recipient T cells eventually induce clonal elimination of Mls-1a reactive V beta 6+, V beta 8.1+ and V beta 9+ T cells derived from developing thymocytes of donor BM origin. The Mls-1a reactive T cells are not eliminated in GVHR chimeras in which recipient T cells are absent. However, V beta 5+ T cells reactive to I-E plus Etc-1 Ag are deleted in the chimeras undergoing GVHR. These results indicate that recipient cells which produce tissue-specific antigens (tolerogens) should be taken into consideration when generation of the T cell repertoire of donor origin following allogeneic BM transplantation is investigated.