Department of Immunology
Anna Valujskikh, Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-5452
Fax: (216) 444-8372
Immunologic memory is the ability of the immune system to respond rapidly and more efficiently to the previously encountered pathogens. While memory T cells are essential for host protection against infections, they can be harmful for life-saving organ transplants. Studies in laboratory animals and humans confirm that the high frequency of donor-reactive memory T cells prior to transplantation correlates with poor allograft outcome. The focus of our group is immunolobiology of memory CD4 T cells in general and the functions of donor-reactive memory CD4 T cells during allograft rejection in particular. We have previously demonstrated that memory CD4 T cells contribute to allograft rejection through multiple pathways. Such a redundancy of effector mechanisms makes controlling memory T cells in alloraft recipient a very challenging problem. Indeed, alloreactive memory T cells appear to be resistant to currently used graft-prolonging strategies including lymphoablation, immunosuppressive drugs and conventional costimulatory blockade. Our ultimate goal is to better understand the functions of graft-reactive memory CD4 T cells in the context of transplantation. This information should enable us to target various aspects of memory T cell response and promote rational development of combinatorial therapies for sensitized transplant recipients.
Schenk, A., Gorbacheva, V., Rabant, M., Fairchild, RL., Valujskikh, A. Effector function of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts. Am. J. Transplantation, 2009, 9:64-73.
Gorbacheva, V., Fan, R., Li, X., Valujskikh, A. Interleukin-17 promotes early allograft inflammation. American Journal of Pathology, 2010, 177:1265-1273.
Sicard A, Phares TW, Yu H, Fan R, Baldwin WM 3rd, Fairchild RL, Valujskikh A. The spleen is the major source of antidonor antibody-secreting cells in murine heart allograft recipients. Am. J. Transplantation, 2012, 12:1708-1719.
Ayasoufi, K., Yu, H., Fan, R., Wang, X., Williams, J.,Valujskikh, A. Pre-transplant antithymocyte globulin has increased efficacy in controlling donor-reactive memory T cells in mice. Am. J. Transplantation, in press.