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.
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.
van Emmerik
N E
NE
Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Loonen
E H
EH
Vaessen
L M
LM
Balk
A H
AH
Mochtar
B
B
Claas
F H
FH
Weimar
W
W
D000915:Antibody Affinity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II