IN-VITRO CYTOKINE PROFILES AND THEIR RELEVANCE TO REJECTION FOLLOWINGRENAL-TRANSPLANTATION

Graft rejection remains an important cause of renal allograft failure, despite improvements in immunosuppression and HLA typing. Although HL A matching is beneficial, ensuring an exact match it is often impracti cal, Thus, a reliable in vitro method for quantitating and qualitating alloreactivity is an important goal. In this study, we measured in vi tro the cytokine secretion profiles of mononuclear cells from patients prior to renal transplantation by stimulating with anti-CD3 monoclona l antibody and suppressing with cyclosporine. Mononuclear cells from p atients who subsequently developed acute cellular rejection secreted h igher mean levels of interleukin (IL)-2 and gamma-interferon (IFN-gamm a) than those from patients who had no rejection episodes. IFN-gamma s ecretion was significantly associated with rejection (P=0.002), wherea s IL-2 secretion did not quite reach statistical significance, There w as no significant correlation between IL-4 levels and rejection. Altho ugh cyclosporine suppressed the secretion of both IL-2 and IFN-gamma, there was no difference in sensitivity to suppression between rejector s and nonrejectors, These results further emphasize the importance of the TH1 lymphocyte subset in renal allograft rejection, The IFN-gamma secretory capacity of alloreactive T cells may influence the outcome o f a renal allograft by (1) activating graft infiltrating macrophages a nd/or (2) up-regulating HLA molecules on the graft.