Preliminary data in the applicant's laboratory have led to the hypothesis that the donor lymphoid cells promote engraftment primarily by recognizing and eliminating or inactivating host lymphocytes that otherwise remain capable of causing rejection. Lymphokines produced by alloactivated T cells may play a subsidiary role but are not sufficient to enable durable engraftment if host lymphocytes are not eliminated. The goals of this proposal are to assess whether donor T cells must exhibit specificity for host alloantigens present restrictively on host lymphoid cells or in cells with non-specific cytotoxic activity mediated graft facilitation. The following specific aims are: 1) to determine whether T cells tolerant to host alloantigens or donor T cells with allospecificity can facilitate engraftment; 2) to determine whether NK cells and activated NK cells can facilitate marrow engraftment without causing GVHD; 3) to assess the abilities of CD4 and/or CD8 cell facilitating engraftment across class I or class II MHC barriers; 4) to assess whether lymphoid cells and hematopoietic cells must be recognized by donor cells to permit graft acceptance; and 5) to test whether alloactivated T cells can accelerate engraftment and increase survival when limited numbers of cells are transplanted in recipients where rejection is not a limiting factor.
| Kusunoki, Y; Chen, W; Martin, P J (1998) Prevention of marrow graft rejection without induction of graft-versus-host disease by a cytotoxic T-cell clone that recognizes recipient alloantigens. Blood 91:4038-44 |
| Martin, P J (1996) Prevention of allogeneic marrow graft rejection by donor T cells that do not recognize recipient alloantigens: potential role of a veto mechanism. Blood 88:962-9 |
| Martin, P J (1995) Influence of alloreactive T cells on initial hematopoietic reconstitution after marrow transplantation. Exp Hematol 23:174-9 |
| Martin, P J (1993) Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans. J Exp Med 178:703-12 |
