THE AVIDITY OF ALLOSPECIFIC CYTOTOXIC T-LYMPHOCYTES (CTL) DETERMINES THEIR CYTOKINE PRODUCTION PROFILE

Donor-specific CTL present within the cardiac allograft during a rejec tion episode are distinct from those that populate the cardiac allogra ft in the absence of rejection. Whereas the former generally have a hi gh avidity for donor cells, the latter mainly have a low avidity for d onor cells. This observation made us reason that high-avidity CTL are implicated in transplant rejection, whereas low-avidity CTL are not. Z n the present study, we analyse whether both CTL subsets were distinct with respect to their IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamm a) secretion pattern. CTL clones with either a high or a low avidity f or donor antigens were stimulated with donor cells, third party cells, or immobilized anti-CD3 MoAb and the amount of cytokine released was measured. High-and low-avidity CTL clones were found to differ with re spect to their IFN-gamma production profile. Stimulation with donor ce lls resulted in IFN-gamma secretion by high-avidity CTL clones, but no t by low-avidity CTL clones. CD3 stimulation, in contrast, led to secr etion of equivalent amounts of IFN-gamma by both CTL subsets. These ob servations indicate that low-avidity CTL are fully capable of producin g IFN-gamma, but, in contrast to high avidity CTL, fail to do so when they encounter donor cells. As IFN-gamma favours the occurrence of tra nsplant rejection, this observation emphasizes the relevance of high-a vidity CTL in the rejection process. Additionally, the data show that the cytokine production profile of CTL depends on the nature of the st imulus.