Abstract
Purified human T lymphocytes, completely depleted of accessory cells [i.e. monocytes, large granular lymphocytes (LGL) and B lymphocytes], have been grown in serum-free culture in presence of a mitogenic lectin (phytohaemagglutinin, PHA) and different recombinant cytokines. Only IL-2 and IL-4 induced a marked stimulation of [3H] thymidine ([3H]TdR) uptake, cell proliferation and expression of activation markers [transferrin receptor (TrfR), IL-2R]. The other cytokines (IL-1α, IL-1β, IFN-γ, GM-CSF, TNF-α) had no significant effect, except for a moderate, but significant, stimulation of [3H]TdR uptake induced by IL-3. Simultaneous addition of IL-4 and anti-IL-2 neutralizing monoclonal antibodies (mAb) did not modify the effects induced by IL-4 alone. Furthermore, IL-2 was not detected in the supernatant of T cells grown in the presence of PHA and IL-4. Thus, our results indicate that IL-4 acts on T lymphocytes independently of IL-2. We also observed that IL-6 moderately activates DNA synthesis in PHA-stimulated T lymphocytes, but markedly potentiates the proliferative effect of suboptimal amounts of IL-2. In conclusion, the present study suggests that B-cell growth factors, in addition to IL-2, control the proliferation of normal circulating T lymphocytes.
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- Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
- Dinarello C. A., Cannon J. G., Mier J. W., Bernheim H. A., LoPreste G., Lynn D. L., Love R. N., Webb A. C., Auron P. E., Reuben R. C. Multiple biological activities of human recombinant interleukin 1. J Clin Invest. 1986 Jun;77(6):1734–1739. doi: 10.1172/JCI112495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harel-Bellan A., Bertoglio J., Quillet A., Marchiol C., Wakasugi H., Mishall Z., Fradelizi D. Interleukin 2 (IL 2) up-regulates its own receptor on a subset of human unprimed peripheral blood lymphocytes and triggers their proliferation. J Immunol. 1986 Apr 1;136(7):2463–2469. [PubMed] [Google Scholar]
- Hirano T., Taga T., Nakano N., Yasukawa K., Kashiwamura S., Shimizu K., Nakajima K., Pyun K. H., Kishimoto T. Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci U S A. 1985 Aug;82(16):5490–5494. doi: 10.1073/pnas.82.16.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hu-Li J., Shevach E. M., Mizuguchi J., Ohara J., Mosmann T., Paul W. E. B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J Exp Med. 1987 Jan 1;165(1):157–172. doi: 10.1084/jem.165.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ihle J. N., Pepersack L., Rebar L. Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine. J Immunol. 1981 Jun;126(6):2184–2189. [PubMed] [Google Scholar]
- Ihle J. N., Weinstein Y., Keller J., Henderson L., Palaszynski E. Interleukin 3. Methods Enzymol. 1985;116:540–552. doi: 10.1016/s0076-6879(85)16042-8. [DOI] [PubMed] [Google Scholar]
- Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., 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] [Google Scholar]
- Kikutani H., Taga T., Akira S., Kishi H., Miki Y., Saiki O., Yamamura Y., Kishimoto T. Effect of B cell differentiation factor (BCDF) on biosynthesis and secretion of immunoglobulin molecules in human B cell lines. J Immunol. 1985 Feb;134(2):990–995. [PubMed] [Google Scholar]
- Kishimoto T. B-cell stimulatory factors (BSFs): molecular structure, biological function, and regulation of expression. J Clin Immunol. 1987 Sep;7(5):343–355. doi: 10.1007/BF00917012. [DOI] [PubMed] [Google Scholar]
- Koide S. L., Inaba K., Steinman R. M. Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells. J Exp Med. 1987 Feb 1;165(2):515–530. doi: 10.1084/jem.165.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lattime E. C., Pecoraro G. A., Stutman O. The activity of natural cytotoxic cells is augmented by interleukin 2 and interleukin 3. J Exp Med. 1983 Mar 1;157(3):1070–1075. doi: 10.1084/jem.157.3.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lichtman A. H., Kurt-Jones E. A., Abbas A. K. 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. doi: 10.1073/pnas.84.3.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malek T. R., Ortega G., Jakway J. P., Chan C., Shevach E. M. The murine IL 2 receptor. II. Monoclonal anti-IL 2 receptor antibodies as specific inhibitors of T cell function in vitro. J Immunol. 1984 Oct;133(4):1976–1982. [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
- Moldwin R. L., Lancki D. W., Herold K. C., Fitch F. W. An antigen receptor-driven, interleukin 2-independent pathway for proliferation of murine cytolytic T lymphocyte clones. J Exp Med. 1986 Jun 1;163(6):1566–1582. doi: 10.1084/jem.163.6.1566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. 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. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noma T., Mizuta T., Rosén A., Hirano T., Kishimoto T., Honjo T. Enhancement of the interleukin 2 receptor expression on T cells by multiple B-lymphotropic lymphokines. Immunol Lett. 1987 Jul;15(3):249–253. doi: 10.1016/0165-2478(87)90032-0. [DOI] [PubMed] [Google Scholar]
- Robb R. J. Human interleukin 2. Methods Enzymol. 1985;116:493–525. doi: 10.1016/s0076-6879(85)16040-4. [DOI] [PubMed] [Google Scholar]
- Royer H. D., Reinherz E. L. T lymphocytes: ontogeny, function, and relevance to clinical disorders. N Engl J Med. 1987 Oct 29;317(18):1136–1142. doi: 10.1056/NEJM198710293171807. [DOI] [PubMed] [Google Scholar]
- Severinson E., Naito T., Tokumoto H., Fukushima D., Hirano A., Hama K., Honjo T. Interleukin 4 (IgG1 induction factor): a multifunctional lymphokine acting also on T cells. Eur J Immunol. 1987 Jan;17(1):67–72. doi: 10.1002/eji.1830170112. [DOI] [PubMed] [Google Scholar]
- Sideras P., Bergstedt-Lindqvist S., MacDonald H. R., Severinson E. Secretion of IgG1 induction factor by T cell clones and hybridomas. Eur J Immunol. 1985 Jun;15(6):586–593. doi: 10.1002/eji.1830150611. [DOI] [PubMed] [Google Scholar]
- Smith K. A., Baker P. E., Gillis S., Ruscetti F. W. Functional and molecular characteristics of T-cell growth factor. Mol Immunol. 1980 May;17(5):579–589. doi: 10.1016/0161-5890(80)90156-x. [DOI] [PubMed] [Google Scholar]
- Spits H., Yssel H., Takebe Y., Arai N., Yokota T., Lee F., Arai K., Banchereau J., de Vries J. E. Recombinant interleukin 4 promotes the growth of human T cells. J Immunol. 1987 Aug 15;139(4):1142–1147. [PubMed] [Google Scholar]
- Taga T., Kawanishi Y., Hardy R. R., Hirano T., Kishimoto T. Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression. J Exp Med. 1987 Oct 1;166(4):967–981. doi: 10.1084/jem.166.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Testa U., Thomopoulos P., Vinci G., Titeux M., Bettaieb A., Vainchenker W., Rochant H. Transferrin binding to K562 cell line. Effect of heme and sodium butyrate induction. Exp Cell Res. 1982 Aug;140(2):251–260. doi: 10.1016/0014-4827(82)90112-4. [DOI] [PubMed] [Google Scholar]
- Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
- Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
- Yokota T., Otsuka T., Mosmann T., Banchereau J., DeFrance T., Blanchard D., De Vries J. E., Lee F., Arai K. Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5894–5898. doi: 10.1073/pnas.83.16.5894. [DOI] [PMC free article] [PubMed] [Google Scholar]