THE EFFECT OF CYCLOSPORINE-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 sens itivity (CS) reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires participation of three distinct T cell subset s: alpha beta(+), CD4(+) T lymphocytes, which are the classical effect or cell of the CS reaction, gamma delta(+) T lymphocytes, and alpha be ta(+), double-negative (CD4(-) CD8(-))T lymphocytes that express the B 220 molecule and produce IL-4. We found that all three drugs inhibit t he development of the CS reaction, but they affect different target ce lls. In fact, rapamycin and FK-506 block both alpha beta(+), CD4(+) an d gamma delta(+) T lymphocytes, while CsA inhibits only the alpha beta (+), CD4(+) T lymphocyte. None of the three drugs exerted any inhibito ry activity on the alpha beta(+), double-negative (CD4(-) CD8(-))T lym phocytes. Hapten-immune lymph node cells from mice treated in vivo wit h CsA or FK506 failed to proliferate and to produce IL-2 when re-expos ed to the specific antigen in vitro. In contrast, immune lymph node ce lls from mice that had been treated in vivo with rapamycin gave optima l antigen-specific proliferation and IL-2 production in vitro. The imp lications of these observations are discussed in relation to the use o f these immunosuppressive agents for prevention of allograft rejection .