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: alphabeta+, CD4+ T lymphocytes, which are the classical effector cell of the CS reaction, gammadelta+ T lymphocytes, and alphabeta+, 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 alphabeta+, CD4+ and gammadelta+ T lymphocytes, while CsA inhibits only the alphabeta+, CD4+ T lymphocyte. None of the three drugs exerted any inhibitory activity on the alphabeta+, 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.
Salerno
A
A
Immunopathology Section, Institute for Advanced Diagnostic Methodologies, CNR, Palermo, Italy.
Bonanno
C T
CT
Caccamo
N
N
Cigna
D
D
Dominici
R
R
Ferro
C
C
Sireci
G
G
Dieli
F
F
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010853:Picryl Chloride; D011090:Polyenes / Q000008:administration & dosage*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D020123:Sirolimus; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D011090:Polyenes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus; D010853:Picryl Chloride