title: Evidence for IL-2 independent proliferation in human T cells.
abstract: Previous models of human T cell proliferation have assumed IL-2 to be largely responsible for the clonal expansion observed after TCR complex (CD3/Ti)-mediated stimulation. By using mAb to the CD3 component of CD3/Ti as well as mAb to other nonpolymorphic T cell surface molecules, we demonstrate T cell proliferation in the absence of detectable IL-2 and define some of the conditions necessary for IL-2 production in vitro. PBL cultured with soluble OKT3 alone or OKT3 plus PMA proliferated nearly equally, but IL-2 was detectable only in the supernatants in the latter condition. RNA blot analyses at 8, 16, and 36 h consistently showed high levels of IL-2 transcripts in the OKT3 + PMA stimulated cells. In contrast, when stimulated with OKT3 alone IL-2 transcripts were barely detectable at the 8-h time point only. Anti-Tac only partially inhibited proliferation induced by either OKT3 or OKT3 + PMA, but consistently prevented it when PBL were stimulated by PMA plus exogenous human rIL-2. Cyclosporin A (CsA) was added in varying doses to PBL cultured in the presence of OKT3 + PMA. At 0.05 microgram/ml, proliferation was only partially inhibited, whereas IL-2 was undetectable. To examine the possibility that IL-4 could account for the observed proliferative response, CsA was added to PBL cultured with either OKT3 alone or OKT3 and PMA. Although IL-4 transcript levels were detectable in the presence of OKT3 alone or OKT3 + PMA, CsA at 0.05 microgram/ml allowed proliferation to occur in the absence of detectable IL-2 as well as IL-2 and IL-4 transcripts. Finally, T cell-enriched PBL were shown to proliferate and also to produce substantial quantities of IL-2 in response to immobilized OKT3 + either OKT11 or 9.3. These results strongly suggest the existence of an IL-2 and IL-4 independent pathway of human T cell proliferation and demonstrate that IL-2 production may result only when a closely defined set of stimuli are present.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
authors.forename: T J
authors.initials: TJ
authors.lastname: Laing
authors.forename: A
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology; D017252:CD3 Complex; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D003524:Cyclosporins; D007376:Interleukin-2; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D013755:Tetradecanoylphorbol Acetate