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.