Murine CD8+ T cell helper function is particularly sensitive to cyclosporine suppression in vivo

In order to investigate the mechanism of action of cyclosporine (CsA) in vivo the drug was used to prolong the survival of different types of allogeneic skin grafts on mice under different conditions. Lower doses of CsA were necessary to prolong class I-disparate grafts than to prolong class II-disparate grafts than to prolong whole MHC-disparate grafts. Second set skin grafts, even of class I-only disparity, could not be prolonged even by higher doses of CsA. Primary class I-disparate grafts, which survived at a low dose of CsA, were rejected at the same dose if a second inducer graft was also placed expressing the same class I Ag plus other mismatched class II Ag. A suboptimal dose of CsA was synergistic with an anti-CD4 mAb but not with an anti-CD8 antibody for whole MHC-mismatched grafts. These results support the notion that CsA interferes with helper T cell function in vivo and suggest that CD8+ helper function is particularly sensitive to CsA suppression.