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Overcoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among pathogen-specific T-cell populations

2010; Lippincott Williams & Wilkins; Volume: 15; Issue: 4 Linguagem: Inglês

10.1097/mot.0b013e32833b7916

1531-7013

Mandy L. Ford, Christian P. Larsen,

Cytomegalovirus and herpesvirus research

Purpose of review 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. Recent findings 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. Summary 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.