Peripheral lymphocyte markers as surrogate measures of immunosuppression and post-transplant clinical states

Abstract

Despite significant improvements in organ transplantation, immunosuppression is associated with rejection or drug toxicity in a significant fraction of transplant recipients. Mechanistic immunological markers may enhance the precision with which immunosuppression, post-transplant alloreactivity and graft adaptation are monitored, and thereby enhance the success of post-transplant immunosuppression. The utility of lymphocyte subset distribution and function as monitoring tools in our laboratory is predicated on observations that: stimulated responses of peripheral blood effector and antigen-presenting lymphocytes (sLR) are inhibited by immunosupressants in a concentration-dependent manner; extended phenotypic monitoring suggests that the memory T-helper population may demonstrate increasing expression of activation marker CD25 (IL-2R) upon contact with transplanted antigen; and donor-specific suppression of costimulatory molecule expression may be mediated by recipient CD8+28− lymphocytes, and is more likely to occur in those with graft adaptation than those who may be prone to rejection. Validation of these observations, and other mechanistic markers may identify newer approaches to monitor the immune system, and reduce efficacy failure with immunosuppression after solid organ transplantation.