Cellular and functional biomarkers of clinical transplant tolerance.

Development of tolerance protocols requires assays or biomarkers that distinguish tolerant recipients from non-tolerant ones to be established. In addition, a thorough understanding of the plausible mechanisms associated with clinical transplant tolerance is necessary to take the field forward. Unlike the majority of molecular signature analyses utilized by others, the emphasis of this article is on the cellular and functional biomarkers of induced transplant tolerance. Immunity to an organ transplant is very complex, comprised of two broad categories - innate and acquired or adaptive immune responses. Innate immunity can be avoided by eliminating or preventing ischemic injuries to the donor organ and tolerance at the level of adaptive immunity can be induced by infusions of a number of cellular products. Since adaptive immune response consists of inflammatory hypersensitivity, cellular (cytotoxic and helper) and humoral aspects, all these need to be measured, and the recipients who demonstrate donor-specific unresponsiveness in all can be considered tolerant or candidates for immunosuppression minimization and/or withdrawal. The mechanisms by which these agents bring about transplant tolerance include regulation, anergy, exhaustion, senescence and deletion of the recipient immune cells. Another proven mechanism of tolerance is full or mixed donor chimerism. However, it should be cautioned that non-deletional tolerance can be reversed.