Alloantibody- 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 several years. We have sought definitive evidence regarding these questions using heart transplants between mouse strains selected to isolate the effects of each form of immune responsiveness.

METHODS

B10.BR hearts were transplanted to B cell-deficient recipients that are devoid of immunoglobulins (muMT). Their vessels were compared with those of transplants 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 recipients 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-positive myointimal cells and little deposition of collagen or ground substance, compared with lesions in fully reactive C57BL/6 recipients in which these changes are prominent. In two other donor-recipient combinations in which anti-donor antibodies are generally undetectable (B10.BR-->B10.A and 129-->C57BL/6), intimal fibrosis was uncommon. However, B10.A recipients became capable of producing fibrous lesions in B10.BR hearts when given anti-donor, class I antibody by passive transfer, as we have observed previously in scid recipients.

CONCLUSIONS

Taken together, these findings indicate that endothelialitis is antibody-independent, whereas antibodies potentiate and can be sufficient for fully developed, fibrous, chronic allograft vasculopathy. Therapeutic strategies for controlling chronic lesions must consider inhibition of the humoral response.