Abstract
This study investigated the production of, and response to, the lymphokine interleukin-2 (IL-2) by functional subsets of human CD4+ T lymphocytes. Fresh peripheral blood mononuclear cells (PBMC) were sorted into CD4+2H4+/4B4- suppressor-inducer cells, and CD4+2H4-/4B4+ helper cells. The suppressor-inducer subset proliferated well in response to the T-cell mitogens concanavalin A (Con) A and phytohaemagglutinin (PHA), and produced IL-2. The helper cells produced no detectable IL-2 and proliferated poorly. However, the latter population were induced to express functional IL-2 receptors by Con A or purified protein derivative (PPD), and proliferated well if supplied with exogenous rIL-2. These findings suggest that the two functional CD4 subsets are not independent, or counteracting, but rather that the generation of T-cell help is likely to involve cooperative interactions between the two subsets.
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- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Alcocer-Varela J., Alarcón-Segovia D. Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus. J Clin Invest. 1982 Jun;69(6):1388–1392. doi: 10.1172/JCI110579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arthur R. P., Mason D. T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation. J Exp Med. 1986 Apr 1;163(4):774–786. doi: 10.1084/jem.163.4.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fernandez-Botran R., Krammer P. H., Diamantstein T., Uhr J. W., Vitetta E. S. B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines. J Exp Med. 1986 Aug 1;164(2):580–593. doi: 10.1084/jem.164.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gearing A. J., Johnstone A. P., Thorpe R. Production and assay of the interleukins. J Immunol Methods. 1985 Oct 24;83(1):1–27. doi: 10.1016/0022-1759(85)90053-5. [DOI] [PubMed] [Google Scholar]
- Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [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]
- Lamb J. R., Zanders E. D., Feldmann M., Lake P., Eckels D. D., Woody J. N., Beverley P. C. The dissociation of interleukin-2 production and antigen-specific helper activity by clonal analysis. Immunology. 1983 Nov;50(3):397–405. [PMC free article] [PubMed] [Google Scholar]
- Linker-Israeli M., Bakke A. C., Kitridou R. C., Gendler S., Gillis S., Horwitz D. A. Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). J Immunol. 1983 Jun;130(6):2651–2655. [PubMed] [Google Scholar]
- Luger T. A., Smolen J. S., Chused T. M., Steinberg A. D., Oppenheim J. J. Human lymphocytes with either the OKT4 or OKT8 phenotype produce interleukin 2 in culture. J Clin Invest. 1982 Aug;70(2):470–473. doi: 10.1172/JCI110637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore K., Nesbitt A. M. Functional heterogeneity of CD4+ T lymphocytes: two subpopulations with counteracting immunoregulatory functions identified with the monoclonal antibodies WR16 and WR19. Immunology. 1987 Jun;61(2):159–165. [PMC free article] [PubMed] [Google Scholar]
- Moretta A. Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning. Eur J Immunol. 1985 Feb;15(2):148–155. doi: 10.1002/eji.1830150208. [DOI] [PubMed] [Google Scholar]
- Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Morimoto C., Steinberg A. D., Letvin N. L., Hagan M., Takeuchi T., Daley J., Levine H., Schlossman S. F. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest. 1987 Mar;79(3):762–768. doi: 10.1172/JCI112882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. 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] [Google Scholar]
- Romain P. L., Morimoto C., Daley J. F., Palley L. S., Reinherz E. L., Schlossman S. F. Reactivity of inducer cell subsets and T8-cell activation during the human autologous mixed lymphocyte reaction. Clin Immunol Immunopathol. 1984 Jan;30(1):117–128. doi: 10.1016/0090-1229(84)90012-6. [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]
- Takeuchi T., Rudd C. E., Schlossman S. F., Morimoto C. Induction of suppression following autologous mixed lymphocyte reaction; role of a novel 2H4 antigen. Eur J Immunol. 1987 Jan;17(1):97–103. doi: 10.1002/eji.1830170117. [DOI] [PubMed] [Google Scholar]
- Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang A., Lu S. D., Mark D. F. Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science. 1984 Jun 29;224(4656):1431–1433. doi: 10.1126/science.6427925. [DOI] [PubMed] [Google Scholar]
- Woollett G. R., Barclay A. N., Puklavec M., Williams A. F. Molecular and antigenic heterogeneity of the rat leukocyte-common antigen from thymocytes and T and B lymphocytes. Eur J Immunol. 1985 Feb;15(2):168–173. doi: 10.1002/eji.1830150211. [DOI] [PubMed] [Google Scholar]