Interleukin-2 does not overcome suppression of graft rejection by cyclosporin A: effect of cyclosporin A on T cell properties in vivo.
The most evident immunosuppressive effect of cyclosporin A (CsA) on T cells is suppression of interleukin-2 (IL-2) production through the suppression of type-2B serine/threonine-specific phosphatase, calcineurin. To test whether suppression of IL-2 production is a major mechanism of CsA-mediated suppression of allograft rejection, we treated allogeneic skin-grafted mice with CsA and IL-2, and observed that IL-2 did not override the suppressive effect of CsA. Specific cytotoxic T lymphocyte (CTL) activity and natural killer (NK) activity of the spleens were increased by treatment with IL-2, and CsA significantly suppressed the killing activity. We also found that CsA-treatment decreased the expression of lck kinase of T cells and the production of IL-2 in response to concanavalin A (ConA), with minimum effect on IL-4 production. These results suggest that T cell dysfunctions other than decreased production of IL-2 are essential for suppressive effect of CsA on skin allograft rejection.
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J
J
Magae
H
H
Matsubara
N
N
Aotsuka
K
K
Kurasawa
G M
GM
Shearer
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases