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J Exp Med. 1993 Nov 1; 178(5): 1645–1653.
PMCID: PMC2191256

CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4

Abstract

Type 1 and type 2 cloned T helper (Th) cells are believed to require different antigen-presenting cell (APC)-derived costimuli for proliferation. In the case of Th1-cloned T cells, CD28 signaling costimulates production of autocrine interleukin 2 (IL-2). Th2 cells produce their autocrine growth factor, IL-4, without costimulation, but require APC-derived costimuli, or IL-1, to respond to IL-4. Here we demonstrate that engagement of CD28 on Th2 cells with anti-CD28 antibody or with APC-associated B7 costimulates Th2 responsiveness to IL-4 but does not affect IL-4 or IL-2 production by Th2 cells. Costimulation of Th2 cells via CD28 appears to involve the induction of IL-1 production by Th2 cells, which acts in an autocrine fashion to induce IL-4 responsiveness. These results suggest that CD28-induced costimulation plays an important role in responses mediated by both types of Th cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed]
  • Kim J, Woods A, Becker-Dunn E, Bottomly K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J Exp Med. 1985 Jul 1;162(1):188–201. [PMC free article] [PubMed]
  • Killar L, MacDonald G, West J, Woods A, Bottomly K. Cloned, Ia-restricted T cells that do not produce interleukin 4(IL 4)/B cell stimulatory factor 1(BSF-1) fail to help antigen-specific B cells. J Immunol. 1987 Mar 15;138(6):1674–1679. [PubMed]
  • Lichtman AH, Kurt-Jones EA, Abbas AK. B-cell stimulatory factor 1 and not interleukin 2 is the autocrine growth factor for some helper T lymphocytes. Proc Natl Acad Sci U S A. 1987 Feb;84(3):824–827. [PMC free article] [PubMed]
  • Jenkins MK, Pardoll DM, Mizuguchi J, Quill H, Schwartz RH. T-cell unresponsiveness in vivo and in vitro: fine specificity of induction and molecular characterization of the unresponsive state. Immunol Rev. 1987 Feb;95:113–135. [PubMed]
  • Quill H, Schwartz RH. Stimulation of normal inducer T cell clones with antigen presented by purified Ia molecules in planar lipid membranes: specific induction of a long-lived state of proliferative nonresponsiveness. J Immunol. 1987 Jun 1;138(11):3704–3712. [PubMed]
  • Lichtman AH, Chin J, Schmidt JA, Abbas AK. Role of interleukin 1 in the activation of T lymphocytes. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9699–9703. [PMC free article] [PubMed]
  • Weaver CT, Hawrylowicz CM, Unanue ER. T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8181–8185. [PMC free article] [PubMed]
  • Kaye J, Gillis S, Mizel SB, Shevach EM, Malek TR, Dinarello CA, Lachman LB, Janeway CA., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed]
  • Damle NK, Hansen JA, Good RA, Gupta S. Monoclonal antibody analysis of human T lymphocyte subpopulations exhibiting autologous mixed lymphocyte reaction. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5096–5098. [PMC free article] [PubMed]
  • Aruffo A, Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. [PMC free article] [PubMed]
  • Thompson CB, Lindsten T, Ledbetter JA, Kunkel SL, Young HA, Emerson SG, Leiden JM, June CH. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333–1337. [PMC free article] [PubMed]
  • Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C, Nadler LM. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6575–6579. [PMC free article] [PubMed]
  • Fraser JD, Irving BA, Crabtree GR, Weiss A. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28. Science. 1991 Jan 18;251(4991):313–316. [PubMed]
  • Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992 Dec 24;71(7):1065–1068. [PubMed]
  • Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. [PubMed]
  • Togawa A, Oppenheim JJ, Mizel SB. Characterization of lymphocyte-activating factor (LAF) produced by human mononuclear cells: biochemical relationship of high and low molecular weight forms of LAF. J Immunol. 1979 May;122(5):2112–2118. [PubMed]
  • Koide S, Steinman RM. Induction of murine interleukin 1: stimuli and responsive primary cells. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3802–3806. [PMC free article] [PubMed]
  • Kaye J, Porcelli S, Tite J, Jones B, Janeway CA., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. [PMC free article] [PubMed]
  • Tony HP, Phillips NE, Parker DC. Role of membrane immunoglobulin (Ig) crosslinking in membrane Ig-mediated, major histocompatibility-restricted T cell-B cell cooperation. J Exp Med. 1985 Nov 1;162(5):1695–1708. [PMC free article] [PubMed]
  • Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. [PMC free article] [PubMed]
  • Gross JA, St John T, Allison JP. The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. J Immunol. 1990 Apr 15;144(8):3201–3210. [PubMed]
  • Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. [PubMed]
  • Ozato K, Mayer N, Sachs DH. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed]
  • Holsti MA, Raulet DH. IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells. J Immunol. 1989 Oct 15;143(8):2514–2519. [PubMed]
  • Kubo RT, Born W, Kappler JW, Marrack P, Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed]
  • Ohara J, Paul WE. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. [PubMed]
  • Mosmann TR, Bond MW, Coffman RL, Ohara J, Paul WE. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Goldman JP, Spencer DM, Raulet DH. Ordered rearrangement of variable region genes of the T cell receptor gamma locus correlates with transcription of the unrearranged genes. J Exp Med. 1993 Mar 1;177(3):729–739. [PMC free article] [PubMed]
  • Evavold BD, Quintans J. Accessory cell function of Th2 clones. J Immunol. 1989 Sep 15;143(6):1784–1789. [PubMed]
  • Evavold BD, Yokoyama A, Hirsch R, Bluestone JA, Quintans J. T helper 2 (Th2) but not Th1 clones co-stimulate resting T cells in the presence of anti-CD3 monoclonal antibody. Int Immunol. 1989;1(4):443–449. [PubMed]
  • Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med. 1991 Mar 1;173(3):721–730. [PMC free article] [PubMed]
  • Bhardwaj N, Lau LL, Friedman SM, Crow MK, Steinman RM. Interleukin 1 production during accessory cell-dependent mitogenesis of T lymphocytes. J Exp Med. 1989 Mar 1;169(3):1121–1136. [PMC free article] [PubMed]
  • Freeman GJ, Freedman AS, Segil JM, Lee G, Whitman JF, Nadler LM. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol. 1989 Oct 15;143(8):2714–2722. [PubMed]
  • Young JW, Koulova L, Soergel SA, Clark EA, Steinman RM, Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992 Jul;90(1):229–237. [PMC free article] [PubMed]
  • Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. [PubMed]
  • Durum SK, Schmidt JA, Oppenheim JJ. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. [PubMed]
  • Lindstein T, June CH, Ledbetter JA, Stella G, Thompson CB. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science. 1989 Apr 21;244(4902):339–343. [PubMed]
  • Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. [PMC free article] [PubMed]
  • Shaw G, Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. [PubMed]
  • Tartakovsky B, Kovacs EJ, Takacs L, Durum SK. T cell clone producing an IL 1-like activity after stimulation by antigen-presenting B cells. J Immunol. 1986 Jul 1;137(1):160–166. [PubMed]
  • Zubiaga AM, Muñoz E, Huber BT. Production of IL-1 alpha by activated Th type 2 cells. Its role as an autocrine growth factor. J Immunol. 1991 Jun 1;146(11):3849–3856. [PubMed]
  • Chiodetti L, Schwartz RH. Induction of competence to respond to IL-4 by CD4+ T helper type 1 cells requires costimulation. J Immunol. 1992 Aug 1;149(3):901–910. [PubMed]
  • Greenbaum LA, Horowitz JB, Woods A, Pasqualini T, Reich EP, Bottomly K. Autocrine growth of CD4+ T cells. Differential effects of IL-1 on helper and inflammatory T cells. J Immunol. 1988 Mar 1;140(5):1555–1560. [PubMed]

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