Modulation of auxiliary signals to T cells as a mechanism to induce transplant tolerance
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Advances in the treatment of transplant rejection, autoimmune disease, allergy, and other conditions of altered immunoregulation have come from our improved knowledge of the multi-faceted nature of lymphocyte activation, incorporating not merely antigen triggering of specific receptors, but a myriad of other accessory signals, all operating within a defined environmental (cytokine) milieu. The review below focuses on just one aspect of this, the ability to manipulate costimulatory signals, or regulatory signals, as a means to induce long-standing immune suppression. Emphasis is placed on the dominant suppression mediated following activation of any one of a number of regulatory signals as a potentially more rational approach to clinical therapy, as the redundancy in costimulatory signals suggests that blockade of any one of these may be unlikely to produce permanent unresponsiveness. The role of regulatory T cells, induced following antigen presentation in the presence of immunoregulatory signals, is also discussed.
Publication order reference
Reginald M. Gorczynski, Transplant Research Division, Toronto Hospital and University Health Network, Toronto, Ontario, Canada