T-Helper Subsets Cytokine Production in Kidney Transplant Recipients: Diverting Influences and Impact on Graft Outcome

A large body of evidence suggests the existence of functionally polarized human T-helper responses based on their profile of cytokine secretion. Human T-helper cell clones can be divided into two mutually exclusive subsets, T-helper cell 1 (Th1) and T-helper cell 2 (Th2). Substantial work in several animal models has demonstrated that allograft rejection is associated with enhanced Th1 activity and tolerance with enhanced Th2. Some studies have not been consistent with this association. In this study, gamma interferon (INF-y) and interleukin 4 (IL-4) levels (as indicators of Th1 and Th2 activity, respectively) were assayed in supernatant of cultured peripheral lymphocytes. The levels of these cytokines were compared between a study group of 26 stable kidney transplant recipients immunosuppressed with cyclosporine A, corticosteroids and azathioprine or mycophenolate mofetil, and a control group of 10 healthy blood donors. The mean INF-γ and IL-4 levels in the control group were considered as the cutoff levels for comparison. Our results showed that 25/26 of the study patients (96%) had low levels of INF-γ compared to 4/10 of the control subjects (40%), (P< 0.05). However, the IL-4 level was high in 10/26 of the study patients (38%) and 3/10 of the control subjects (30%), not a statistically significant difference, (P>0.05). In conclusion: These results suggest that well-established graft tolerance may be mediated via depressed Th1 activity rather than enhanced Th2 activity