During the past year we continued our collaborations with Katy Rezvani, Stephan Rezvani and John Barrett focusing on the role of donor derived suppressor T cells on immune responses after allotransplantation. Using sophisticated flow cytometric methods for distinguishing between activated human CD4 effector (CD4+,CD25+, FoxP3-) T cells and CD4 regulatory (CD4+, FoxP3+) T cells, these studies made two important points. First, they could show a strong inverse association between the level of donor-derived CD4 suppressor cells generated by day 30 post transplant, and the level of GVHD in the early post-transplant period. Second, they demonstrated that selective depletion protocols designed to remove CD25+ effector cells from donor Tcell preparations do not adversely affect the regeneration of these CD4 T regulatory cells in vivo. In sum, the studies support an important role for suppressor populations in determining the incidence of GVHD, and they also suggest the level of suppressor cells in the donor stem cell preparation used for engraftment may be an independent determinant of suppressor T cell recovery and GVHD posttransplant. We have also continued studies with Dr. Childs laboratory studying the CD8 T cell response against the tumor specific antigen, CT-RCC expressed in patients with renal cell carcinoma (RCC). RCC patients expressing HLA-A11 generate a CD8 T cell response directed against a defined immunogenic peptide within the CT-RCC molecule. To establish the immunogenicity of this peptide, and to generate peptide specific CD8 T cell lines which can be used for in vitro studies, we used CT-RCC pulsed dendritic cells to generate peptide specific celll lines from normal HLA-A11 individuals. Multiple cell lines have been generated, and these are curently being activity characterized.
| Rezvani, Katayoun; Yong, Agnes S M; Tawab, Abdul et al. (2009) Ex vivo characterization of polyclonal memory CD8+ T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia. Blood 113:2245-55 |
| Takahashi, Yoshiyuki; Harashima, Nanae; Kajigaya, Sachiko et al. (2008) Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells. J Clin Invest 118:1099-109 |
| Mielke, Stephan; Rezvani, Katayoun; Savani, Bipin N et al. (2007) Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantation in elderly patients and association with acute graft-versus-host disease. Blood 110:1689-97 |
| Rezvani, Katayoun; Mielke, Stephan; Ahmadzadeh, Mojgan et al. (2006) High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 108:1291-7 |
