Direct effect of cyclosporin A on CD8+ T lymphocytes in a primary mixed lymphocyte reaction.
Cyclosporin A (CsA) blocks the development of cytotoxic T lymphocytes (CTL) in a primary mixed lymphocyte reaction (MLR) when added during the first few days of culture. We found that addition of recombinant IL-2 (rIL-2) or an IL-2-containing supernatant (2 degrees MLR SN) either alone or in combination was unable to reverse the suppression. Purified CD8+ responder cells were inhibited as effectively by CsA as unfractionated cells, suggesting that CsA has a direct, lymphokine-independent effect on CD8+ cells. The frequency of CTL precursors (CTLp) responding in a primary MLR was measured by limiting dilution in the presence and absence of CsA. Using either unfractionated cells or cell-sorter-purified CD8+ responder cells, no suppression was seen at very low cell numbers but increased markedly as the cell number per culture increased. These results imply that either a CD8+ regulatory/suppressor cell is being diluted out at low cell numbers, or that low cell-density culture conditions might override the inhibitory effects of CsA.
Kiziroglu
F
F
Department of Immunology, University of Toronto, Ontario, Canada.
Miller
R G
RG
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D003524:Cyclosporins; D003907:Dexamethasone