Effect of cyclosporin and interleukin-2 on the restoration of in vitro immune responses to cytomegalovirus.
Previous studies have shown that cyclosporin (CSA) inhibits lymphoproliferation to cytomegalovirus (CMV)-infected, glutaraldehyde-fixed, and irradiated fibroblasts (CMVFFx) in vitro. Generation of cytotoxic cell activity is impaired in cultures with CSA, but the induction of suppressor cells is not. In the present studies we tested the ability of interleukin-2 (IL-2) and supernatants of lymphocytes stimulated by CMVFFx with or without CSA (1 microgram/ml) to restore functional activities of lymphocytes from primary cultures treated or not treated with CSA. IL-2 significantly enhanced lymphoproliferation, cell-mediated cytotoxicity to CMV-infected fibroblasts (CMVF), natural killer cell activity, and the activity of cells capable of suppressing the response of fresh autologous cells to CMVFFx of cells derived from control and CSA-treated primary cultures. IL-2 was found in day-2 supernatants of control cultures but not CSA-treated cultures. Day-2 control supernatants were capable of significantly enhancing proliferation and suppressor cell activity but were less efficient at restoring cytotoxic cell function. Day-2 supernatants from CSA-treated cultures were not able to enhance lymphoproliferation or cytotoxic cell function but did induce significant levels of suppressor cell activity. The results indicate the presence of different functional mediators in the culture supernatants. The ability of IL-2 to restore lymphocyte effector functions against a clinically important virus may have important therapeutic implications in the treatment of this viral infection in immunodeficiency diseases and in the restoration of immune competence after transplantation.
Converse
P J
PJ
Hess
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D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D003524:Cyclosporins; D007376:Interleukin-2