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The Journal of Immunology, Vol 140, Issue 10 3303-3308, Copyright © 1988 by American Association of Immunologists


ARTICLES

Cyclosporine blocks the activation of antigen-dependent cytotoxic T lymphocytes directly by an IL-2-independent mechanism

C Havele and V Paetkau
Department of Biochemistry, University of Alberta, Edmonton, Canada.

The immunosuppressive drug Cyclosporin A (cyclosporine) inhibits the reactivation of quiescent Ag-dependent CTL in the presence of IL-2. Both proliferation and the regeneration of cytotoxicity are inhibited. The cytotoxic cells that are inhibited are Ag dependent for activation, whereas derived, Ag-independent, but still IL-2-dependent, cytotoxic cells are insensitive to cyclosporine. Cyclosporine also directly inhibits the effector phase of the cytotoxic cells, although not completely. The generation of primary CTL in mixed cultures was also blocked by cyclosporine in the presence of IL-2, in a time-dependent way that indicated that the sensitive time was early during the cultures. The CTL generated in primary cultures were significantly inhibited by cyclosporine in the assay, but this inhibition was less than for the cloned CTL lines.


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M. Jenkins, R. Schwartz, and D. Pardoll
Effects of cyclosporine A on T cell development and clonal deletion
Science, September 23, 1988; 241(4873): 1655 - 1658.
[Abstract] [PDF]




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