ALLOANTIBODY-IMMUNITY AND T-CELL-MEDIATED-IMMUNITY IN THE PATHOGENESIS OF TRANSPLANT ARTERIOSCLEROSIS - LACK OF PROGRESSION TO SCLEROTIC LESIONS IN B-CELL-DEFICIENT MICE

Background The relative roles of humoral and cell-mediated immunity in generating chronic allograft arteriopathy have been considered for se veral years. We have sought definitive evidence regarding these questi ons using heart transplants between mouse strains selected to isolate the effects of each form of immune responsiveness. Methods. B10.BR hea rts were transplanted to B cell-deficient recipients that are devoid o f immunoglobulins (mu MT). Their vessels were compared with those of t ransplants to fully reactive recipients of the same genetic background (C57BL/6). Additional evidence came from comparisons in other strain combinations.Results. Transplants to B cell-deficient and normal recip ients developed cellular coronary endothelialitis, with destruction of the arterial media, accompanied by the adherence of T lymphocytes and macrophages to endothelial surfaces. In B cell-deficient recipients, there was no centripetal migration of smooth muscle, alpha-actin-posit ive myointimal cells and little deposition of collagen or ground subst ance, compared with lesions in fully reactive C57BL/6 recipients in wh ich these changes are prominent. In two other donor-recipient combinat ions in which anti-donor antibodies are generally undetectable (B10.BR -->B10.A and 129-->C57BL/6), intimal fibrosis was uncommon. However, B 10.A recipients became capable of producing fibrous lesions in BIO,BR hearts when given anti-donor, class I antibody by passive transfer, as we have observed previously in scid recipients. Conclusions. Taken to gether, these findings indicate that endothelialitis is antibody-indep endent, whereas antibodies potentiate and can be sufficient for fully developed, fibrous, chronic allograft vasculopathy. Therapeutic strate gies for controlling chronic lesions must consider inhibition of the h umoral response.