- Dr Emilio Poggio, Principal Investigator
- Assoc. Prof. Joshua Augustine, Co-Investigator
- Dr Jesse Schold Co-Investigator
- Dr Opas Traitanon, Research Associate
- Dr Robert Fairchild, Consultant
- Cleveland Clinic, Cleveland, USA
- Role of a Subtype of Memory T Cells in Immune Rejection of Transplanted Kidneys
Despite recent advances in immunosuppression, rejection of transplanted kidneys by recipient patients’ cellular immune responses remains a significant problem. Central effectors of immune rejection are memory T cells, which are generated in response to initial exposure to a foreign antigen, and proliferate rapidly and potently when re-exposed to the antigen. Presumably, memory T cells generated previously against a particular foreign antigen cross react with one or more similar antigens on transplanted organs. While many memory T cells express the co-stimulatory molecule CD28, a cell surface receptor in a T cell-activation signaling pathway that is the target of a novel immunosuppressive therapy, we are studying a subtype of memory T cells that do not express CD28, and thus are not responsive to that novel therapy. The subtype of cells we are studying do express the receptor NKG2D, which is suspected to be a contributor to transplant rejection and might provide a new therapeutic target. Improved immunosuppression will require a better understanding of the role of these CD28null/NKG2Dpos memory T cells in rejection of transplanted organs. Therefore, we propose to study 80 kidney transplant recipients who have provided or will provide blood and biopsy specimens, in order to characterize their CD28null/NKG2Dpos cells in terms of: a) the prevalence and proportion of those cells among all of the memory T cells at the time of transplantation; b) the potency of activation of the cells by non-self human antigens, and the role of NKG2D in the activation; c) the effects of different T cell-depleting “induction therapies” on the prevalence of the cells; and d) the correlation of CD28null/NKG2Dpos cell frequency with the histological condition and function of the transplanted kidney. The results of our studies will provide novel insights into the understanding of T cell-mediated transplant injury and rejection, and may uncover novel targets for more effective immunosuppressive therapy.