IMMUNOLOGICAL BASIS OF TRANSPLANT-ASSOCIATED ARTERIOSCLEROSIS

Although immunosuppressive therapy minimizes the risk of graft failure due to acute rejection, transplant-associated arteriosclerosis of the coronary arteries remains a significant obstacle to the long-term sur vival of heart transplant recipients. The participation of specific in flammatory cell types in the genesis of this lesion was examined in a mouse model in which carotid arteries were transplanted across multipl e histocompatibility barriers into seven mutant strains with immunolog ic defects. An acquired immune response-with the participation of CD4( +) (helper) T cells, humoral antibody, and macrophages-was essential t o the development of the concentric neointimal proliferation and lumin al narrowing characteristic of transplant arteriosclerosis. CD8(+) (cy totoxic) T cells and natural killer cells were not involved in the pro cess. Arteries allografted into mice deficient in both T-cell receptor s and humoral antibody showed almost no neointimal proliferation, wher eas those grafted into mice deficient only in helper T cells, humoral antibody, or macrophages developed small neointimas. These small neoin timas and the large neointimas of arteries grafted into control animal s contained a similar number of inflammatory cells; however, smooth mu scle cell number and collagen deposition were diminished in the small neointimas. Also, the degree of inflammatory reaction in the adventiti a did not correlate with the size of the neointima. Thus, the reductio n in neointimal size in arteries allografted into mice deficient in he lper T cells, humoral antibody, or macrophages may be accounted for by a decrease in smooth muscle cell migration or proliferation.