Overcoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among pathogen-specific T-cell populations.
OBJECTIVE
This review highlights recent advances in our understanding of the frequency and nature of alloreactivity among memory T-cell populations, and discusses recent successes in experimentally targeting these populations in order to prolong graft survival.


RESULTS
Recent studies suggest that not only is alloreactivity present within peripheral T-cell compartments of normal healthy individuals, but cross-reactivity between viral-specific T cells and allotropes may in fact be a very common occurrence. Furthermore, this cross-reactivity functions at the level of molecular mimicry of T-cell receptor recognition. Therapeutics that specifically target cell surface molecules or effector pathways used by memory T cells to mediate graft rejection will likely be required in order to attenuate the donor-reactive memory T-cell response during transplantation.


CONCLUSIONS
A major challenge facing the field over the next decade is to define the heterogeneity that exists within memory T-cell populations that impacts graft survival. Understanding the functional and phenotypic differences that modify the memory T-cell barrier to tolerance induction might allow a strategy in which strength of immunosuppression could be tailored to fit the immunological history of a given transplant recipient in order to minimize nonimmune toxicities, maximize protective immunity, and prolong graft survival.
Ford
Mandy L
ML
Department of Surgery, Emory Transplant Center, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
Larsen
Christian P
CP
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D003429:Cross Reactions; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018716:Molecular Mimicry; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance; D014777:Virus Diseases / Q000276:immunology
D000956:Antigens, Viral; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell