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Anna Valujskikh, Ph.D.
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Area of general research interest:
- Transplant Immunology
- Memory T Cells
- T Cell Costimulation
Current program:
- Function of memory CD4 T cells in allograft rejection
- Controlling memory CD4 T cells in organ transplant recipients
- T cell recruitment into transplanted organ
- Alternative costimulatory pathways in allograft rejection
Investigators:
- Earla Biekert, BA, Laboratory Manager
- Victoria Gorbacheva, Lead Technologist
- Marion Rabant, MD, Research Fellow
- Qi-Wei Zhang, MD Research Fellow
Collaborators:
- Robert Fairchild, PhD, Department of Immunology, Cleveland Clinic
- Angus Thomson, PhD, University of Pittsburgh Medical Center, Pittsburgh PA
Brief Description:
Immunologic memory is the ability of the immune system to respond rapidly and more efficiently to new attacks by previously encountered pathogens. Although memory T cells are essential for host protection against infections, they can be harmful to 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 immunobiology of memory CD4 T cells in general and the functions of donor-reactive memory CD4 T cells during allograft rejection in particular.
We have 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 allograft recipients a very challenging problem. Indeed, alloreactive memory T cells appear to be resistant to graft-prolonging strategies, including lymphoablation, immunosuppressive drugs and conventional co-stimulatory 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.
Key References:
Valujskikh A, Pantenburg B, Heeger PS. Primed allospecific T cells prevent the effects of costimulatory blockade on prolonged cardiac allograft survival in mice. American Journal of Transplantation, 2002, 2(6):501-9.
Pantenburg B, Heizel F, Das L, Heeger PS, Valujskikh A. T cells primed by Leishmania major infection cross-react with alloantigens and alter the course of allograft rejection. Journal of Immunology, 2002,169(7):3686-93.
Valujskikh A, Lakkis FG. In remembrance of things past: memory T cells and transplant rejection. Immunological Reviews, 2003, 196:65-74.
Chen Y, Heeger PS, Valujskikh A. In vivo helper functions of alloreactive memory CD4+ T cells remain intact despite donor-specific transfusion and anti-CD40 ligand therapy. Journal of Immunology, 2004, 172(9):5456-66.
Zhang Q, Chen Y, Fairchild RL, Heeger PS, Valujskikh A. Lymphoid sequestration of alloreactive memory CD4 T cells promotes cardiac allograft survival. Journal of Immunology, 2006, 176(2):770-7.
Valujskikh A. The challenge of inhibiting alloreactive T-cell memory. American Journal of Transplantation, 2006, 6(4):647-51.
Valujskikh A, Zhang Q, Heeger PS. CD8 T cells specific for a donor-derived, self-restricted transplant antigen are nonpathogenic bystanders after vascularized heart transplantation in mice. Journal of Immunology, 2006;176:2190-6.
Zhang Q, Rabant M, Schenk A, Valujskikh A. ICOS-dependent and independent functions of memory CD4 T cells in allograft rejection. American Journal of Transplantation, 2008, 8:497-506