The effect of cyclosporin A,FK506 and rapamycin on the murine contact sensitivity reaction

We have evaluated the effects of three potent immunosuppressive agents, cyclosporin A (CsA), FK506 and rapamycin, on the murine contact sensitivity (CS) reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires participation of three distinct T cell subsets: αβ⁺, CD4⁺ T lymphocytes, which are the classical effector cell of the CS reaction, γδ⁺ T lymphocytes, and αβ⁺, double-negative (CD4^? CD8^?) T lymphocytes that express the B220 molecule and produce IL-4. We found that all three drugs inhibit the development of the CS reaction, but they affect different target cells. In fact, rapamycin and FK-506 block both αβ⁺, CD4⁺ and γδ⁺ T lymphocytes, while CsA inhibits only the αβ⁺, CD4⁺ T lymphocyte. None of the three drugs exerted any inhibitory activity on the αβ⁺, double-negative (CD4^? CD8^?) T lymphocytes. Hapten-immune lymph node cells from mice treated in vivo with CsA or FK506 failed to proliferate and to produce IL-2 when re-exposed to the specific antigen in vitro. In contrast, immune lymph node cells from mice that had been treated in vivo with rapamycin gave optimal antigen-specific proliferation and IL-2 production in vitro. The implications of these observations are discussed in relation to the use of these immunosuppressive agents for prevention of allograft rejection.