POSITIVE CORRELATION OF T CELL SENSITIZATION WITH FREQUENCIES OF ALLOREACTIVE T HELPER CELLS IN CHRONIC RENAL FAILURE PATIENTS

Chronic renal failure patients are often "sensitized" to foreign alloantigens following renal transplantation or blood transfusion. B cell sensitization is assessed by measuring the reactivity of cytotoxic antibodies in the patient's serum against a panel of allogeneic cells (panel-reactive antibodies, [PRA]). However, this technique provides no information about T cell allosensitization. T cell allosensitization may be important since T cells play a central role in allograft rejection and since "primed" alloreactive cells--i.e., T cells that have previously encountered their specific alloantigen, are relatively resistant to immunosuppression. In order to detect T cell sensitization we used a limiting dilution analysis assay, which measured both total and primed frequencies of alloreactive T helper (Th) cells. Total alloreactive Th cell frequencies were generally high. Primed alloreactive Th cell frequencies could be detected in all patients studied, although there was considerable variation in frequencies between different patients. Frequencies of primed Th cells did not correlate with levels of PRA. However, in all three of the patients who had received DR-mismatched kidneys, and who had subsequently rejected these grafts rapidly, high primed frequencies were detected against the mismatched DR antigens. This was not the case for two patients who had lost their grafts two or more years after transplantation.