INFLUENCE OF GRAFT-VERSUS-HOST REACTION ON THE T-CELL REPERTOIRE DIFFERENTIATING FROM BONE-MARROW PRECURSORS FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION

When lethally irradiated AKR (Mls-1(a)) mice were reconstituted with b one marrow (BM) cells plus a small number (0.5%) of mature T cells fro m allogeneic B10.AQR or B10 (Mls-1(b)) mice and minor GVHR was induced in the recipients, almost complete donor chimerism was accomplished i n the early stages after reconstitution. By contrast, in irradiated AK R mice reconstituted with T cell-depleted BM cells alone from B10 or B 10.AQR mice, radio-resistant T cells of recipient origin persisted for a relatively long period in peripheral lymphoid tissues. In this pape r 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 produc ing Mls-la antigens (Ag) after lethal irradiation in vivo. These recip ient T cells eventually induce clonal elimination of Mls-1(a) reactive V beta 6(+), V beta 8.1(+) and V beta 9(+) T cells derived from devel oping thymocytes of donor BM origin. The Mls-1(a) 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 delet ed in the chimeras undergoing GVHR. These results indicate that recipi ent cells which produce tissue-specific antigens (tolerogens) should b e taken into consideration when generation of the T cell repertoire of donor origin following allogeneic BM transplantation is investigated.