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  • Title: The avidity, not the mere presence, of primed cytotoxic T-lymphocytes for donor human leukocyte class II antigens determines their clinical relevance after heart transplantation.
    Author: van Emmerik NE, Loonen EH, Vaessen LM, Balk AH, Mochtar B, Claas FH, Weimar W.
    Journal: J Heart Lung Transplant; 1997 Feb; 16(2):240-9. PubMed ID: 9059936.
    Abstract:
    BACKGROUND: To analyze the relevance of CD4-positive cytotoxic T-lymphocytes (CTL) in clinical heart rejection, we studied the frequency and avidity of donor human leukocyte antigen class II-specific CTL present within the graft during a rejection episode and during a period without rejection. METHODS: For this analysis endomyocardial biopsies of heart transplant recipients were cultured to obtain graft-infiltrating lymphocytes (GIL). GIL cultures exhibiting donor class II-directed cytotoxicity were considered for this study. With limiting dilution analysis, the frequency of donor class II-specific CTL that had been primed by donor antigens in vivo (designated cCTL) was determined in GIL cultures established from endomyocardial biopsies taken during a rejection episode (n = 10) or during a period without rejection (n = 11). Addition of anti-CD4 to the limiting dilution analysis revealed the fraction of donor class II-specific cCTL having a high avidity for donor antigen. RESULTS: During a rejection episode, 196 (median) donor class II-specific cCTL/106 GIL were present. In a period without rejection, the frequency of donor class II-specific cCTL was not significantly different (median = 330/10(6); p = 0.1). Addition of anti-CD4, however, revealed that donor class II-specific cCTL with a high avidity for donor antigen are predominant during a rejection episode (median = 100%) but are in minority during a period without rejection (median = 35%; p < 0.0001). CONCLUSIONS: These results suggest that graft-infiltrating CD4+ CTL can mediate heart rejection provided they have a high avidity for donor antigen.
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