In vitro modulation of human, autoreactive MBP-specific CD4 + T-cell clones by cyclosporin A.
Cyclosporin A (CsA) is a potent immunosuppressant affecting many components of cellular and humoral immunity. Its main action probably results from inhibition of T-lymphocyte activation and interference with secretion of cytokines like IL-2, IL-4, IFN-gamma and TNF-alpha. Correspondingly, CsA has beneficial effects on the course of several autoimmune diseases thought to be mediated by T-lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4 + cytotoxic T-lymphocytes specific for myelin basic protein, a putative target autoantigen in MS, to CsA in vitro, and determined the drug's effects on proliferation, expression of high affinity IL-2R, secretion of the proinflammatory cytokines IFN-gamma and TNF-alpha as well as on the secretion of the chemokines MIP-1 alpha and MIP-1 beta. In all instances, we observed a partial to complete inhibition. In contrast, the response of activated cells to IL-2 was resistant to CsA. Our observations are in line with results obtained in different experimental systems. The discrepancy between the profound inhibition of T-cells and the modest therapeutic effects on MS is discussed.
Pette
M
M
Neuroimmunology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA. mpette@box-m.nih.gov
Pette
D F
DF
Muraro
P A
PA
Martin
R
R
McFarland
H F
HF
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D004676:Myelin Basic Protein; D016572:Cyclosporine