The long term goal of this project is to identify a population of donor T cells that can be used to prevent graft rejection without significant graft versus host disease after allogeneic bone marrow transplantation. In order to assess the feasibility of using CD8 cells to assure engraftment without causing GVHD, the phenotype and function of donor CD8+ T cells must be established. The investigator will test: (1) whether the desired cell must be cytotoxic, (2) whether alloantigens expressed only on lymphohematopoietic cells are more effective targets than broadly expressed alloantigens, (3) whether T cells with low affinity TCR are better than T cells with high affinity TCR, and (4) whether donor T cells must migrate and home to lymph nodes in order to prevent rejection. In addition, the role of alloimmunization of the recipient will be tested. Identification of a CD8 population that can prevent rejection without causing GVHD in mice will lead to the testing of similar approaches in humans. These results will be of importance not only for allogeneic bone marrow transplantation but also for the design of novel adoptive immunotherapies.
|Kozaki, Koichi; Kaminski, Wolfgang E; Tang, Jingjing et al. (2002) Blockade of platelet-derived growth factor or its receptors transiently delays but does not prevent fibrous cap formation in ApoE null mice. Am J Pathol 161:1395-407|
|Kaminski, W E; Lindahl, P; Lin, N L et al. (2001) Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF beta-receptor null mice. Blood 97:1990-8|
|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; Akatsuka, Y; Hahne, M et al. (1998) Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. Blood 92:2177-81|