Induction of cytotoxic T lymphocytes with destructive potential after cardiac valve homograft implantation.
OBJECTIVE
Clinical and experimental studies have shown that a specific immunological response may play a role in the degeneration of human cardiac valve homografts. In heart and corneal transplantation, cytotoxic T lymphocytes (CTL) with high avidity for donor antigens are presumed to be the major effector cells causing graft destruction. We studied the kinetics of these donor-specific CTL precursors (CTLp) and their high-avidity fraction in peripheral blood of patients receiving a cryopreserved valve homograft.


METHODS
Limiting dilution analysis (LDA) was used to enumerate donor-specific CTLp in peripheral blood samples of 15 patients, obtained up to 12 months after valve implantation. Donor-specificity was proven by using donor-HLA mismatched third-party stimulation cells as controls. CD8 monoclonal antibodies were used to distinguish high- and low-avidity CTLp.


RESULTS
A significant increase in total donor-specific CTLp among the peripheral blood mononuclear cell population occurred in 14/15 patients (93%) at 3-6 months (p = 0.045) after implantation and remained so for up to 12 months (p = 0.015). In addition, a significant increase was seen in the fraction of circulating CTLp with high avidity for donor antigens (p<0.026) within the first 3 months after implantation.


CONCLUSIONS
Implantation of cryopreserved valve homografts increases the number of donor-specific CTLp and their high-avidity fraction, in the peripheral blood. These cells have the capacity to destroy organ and tissue grafts.
Oei FBS
Department of Thoracic Surgery, University Hospital Rotterdam, The Netherlands.
Welters
M J
MJ
Vaessen
L M
LM
Stegmann
A P
AP
Bogers
A J
AJ
Weimar
W
W
D000293:Adolescent; D000328:Adult; D001021:Aortic Valve / Q000637:transplantation; D016827:CD8 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015925:Cryopreservation; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006351:Heart Valves / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D011664:Pulmonary Valve / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D007519:Isoantigens