Immunoregulation and production of tumor necrosis factor alpha by human thymocytes.
We have provided evidence that tumor necrosis factor alpha (TNF-alpha) enhances the proliferation and the state of activation of human thymocytes cultured with concanavalin A or interleukin 2 (IL-2), as evidenced by an increase in the expression of the c-myc gene and the gene of the IL-2 receptor (alpha-chain, Tac antigen) and by the expression of Tac antigen on the cell surface. Our observations suggest that TNF-alpha interacts with IL-2 and with another factor(s) which is induced in the course of activation by concanavalin A, since the immunosuppressant drug cyclosporin A-, which inhibits thymocyte activation, prevents the effect of TNF-alpha on thymocytes activated with concanavalin A, whereas anti-Tac, which prevents the binding of IL-2 to its receptor without affecting the production of IL-2 or the expression of IL-2-specific mRNA, inhibits proliferation only partially. By contrast, anti-Tac inhibits the response to TNF-alpha of thymocytes induced with IL-2 completely. These observations show that TNF-alpha exerts a potentially important immunoregulatory effect in synergy with IL-2 on thymocytes, which could contribute to tumor rejection. In addition, we show that activated human thymocytes express the TNF-alpha gene and that the expression of this gene is inhibited by cyclosporin A and dexamethasone.
Reem
G H
GH
Department of Pharmacology, New York University Medical Center, New York 10016.
Duggan
A
A
Schleuning
M
M
D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D003524:Cyclosporins; D007295:Inositol Phosphates; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A