The avidity of allospecific cytotoxic T lymphocytes (CTL) determines their cytokine production profile.

Abstract:

:Donor-specific CTL present within the cardiac allograft during a rejection episode are distinct from those that populate the cardiac allograft in the absence of rejection. Whereas the former generally have a high avidity for donor cells, the latter mainly have a low avidity for donor cells. This observation made us reason that high-avidity CTL are implicated in transplant rejection, whereas low-avidity CTL are not. In 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-gamma) secretion pattern. CTL clones with either a high or a low avidity for 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 respect to their IFN-gamma production profile. Stimulation with donor cells resulted in IFN-gamma secretion by high-avidity CTL clones, but not by low-avidity CTL clones. CD3 stimulation, in contrast, led to secretion of equivalent amounts of IFN-gamma by both CTL subsets. These observations indicate that low-avidity CTL are fully capable of producing 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 transplant rejection, this observation emphasizes the relevance of high-avidity CTL in the rejection process. Additionally, the data show that the cytokine production profile of CTL depends on the nature of the stimulus.

journal_name

Clin Exp Immunol

authors

Van Emmerik NE,Daane CR,Knoop CJ,Hesse C,Vaessen LM,Balk AH,Mochtar B,Claas FH,Weimar W

doi

10.1046/j.1365-2249.1997.4441458.x

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

447-53

issue

3

eissn

0009-9104

issn

1365-2249

journal_volume

110

pub_type

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