title: 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.
authors.affiliation: Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
authors.forename: N E
authors.initials: NE
authors.lastname: Van Emmerik
authors.forename: C R
authors.initials: CR
authors.lastname: Daane
authors.forename: C J
authors.initials: CJ
authors.lastname: Knoop
authors.forename: C
authors.initials: C
authors.lastname: Hesse
authors.forename: L M
authors.initials: LM
authors.lastname: Vaessen
authors.forename: A H
authors.initials: AH
authors.lastname: Balk
authors.forename: B
authors.initials: B
authors.lastname: Mochtar
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007371:Interferon-gamma