Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1985 Oct;62(1):112–120.

OKT4+ and OKT8+ T lymphocytes produce soluble factors that can modulate growth and differentiation of human B cells.

T Sakane, Y Ueda, N Suzuki, Y Niwa, T Hoshino, T Tsunematsu
PMCID: PMC1577404  PMID: 3933868

Abstract

The human T cell subset(s) responsible for the production of soluble factors that can modulate B cell growth and B cell differentiation was investigated in the present study. For this purpose, highly purified OKT4+ and OKT8+ lymphocytes were stimulated with phytohaemagglutinin and phorbol myristate acetate. Subsequently, culture supernatants were analysed for B cell growth factor (BCGF) activity and B cell differentiation factor (BCDF) activity in the following systems: 1) maintenance of a proliferative state of Staphylococcus aureus of strain Cowan I (SAC)-stimulated B cells and 2) induction of plaque-forming cell responses of SAC-stimulated B cells. Mitogenic stimulation led to production of equivalent amounts of either BCGF activity or BCDF activity from both of the OKT4+ and OKT8+ subsets. These findings may provide a basis for further studies of the molecular mechanisms as well as cellular interactions involved in human B cell activation, proliferation and differentiation.

Full text

PDF
112

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bensussan A., Meuer S. C., Schlossman S. F., Reinherz E. L. Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones. J Exp Med. 1984 Feb 1;159(2):559–576. doi: 10.1084/jem.159.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J Exp Med. 1982 Oct 1;156(4):1065–1076. doi: 10.1084/jem.156.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Damle N. K., Hansen J. A., Good R. A., 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. doi: 10.1073/pnas.78.8.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dutton R. W. Separate signals for the initiation of proliferation and differentiation in the b cell response to antigen. Transplant Rev. 1975;23:66–77. doi: 10.1111/j.1600-065x.1975.tb00149.x. [DOI] [PubMed] [Google Scholar]
  5. Engleman E. G., Benike C. J., Grumet F. C., Evans R. L. Activation of human T lymphocyte subsets: helper and suppressor/cytotoxic T cells recognize and respond to distinct histocompatibility antigens. J Immunol. 1981 Nov;127(5):2124–2129. [PubMed] [Google Scholar]
  6. Falkoff R. J., Zhu L. P., Fauci A. S. Separate signals for human B cell proliferation and differentiation in response to Staphylococcus aureus: evidence for a two-signal model of B cell activation. J Immunol. 1982 Jul;129(1):97–102. [PubMed] [Google Scholar]
  7. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  8. Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
  9. Kotani H., Takada S., Ueda Y., Murakawa Y., Suzuki N., Sakane T. Activation of immune regulatory circuits among OKT4+ cells by autologous mixed lymphocyte reactions. Clin Exp Immunol. 1984 May;56(2):390–398. [PMC free article] [PubMed] [Google Scholar]
  10. Krensky A. M., Reiss C. S., Mier J. W., Strominger J. L., Burakoff S. J. Long-term human cytolytic T-cell lines allospecific for HLA-DR6 antigen are OKT4+. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2365–2369. doi: 10.1073/pnas.79.7.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lehner T., Brines R., Jones T., Avery J. Detection of cross-reacting murine I-J like determinants on a human subset of T8+ antigen binding, presenting and contrasuppressor cells. Clin Exp Immunol. 1984 Nov;58(2):410–419. [PMC free article] [PubMed] [Google Scholar]
  12. Lehner T., Jones T. The role of MHC class II antigenic determinants in the function of human antigen binding T8+ cells, monocytes and helper and suppressor factors. Clin Exp Immunol. 1984 Jun;56(3):683–693. [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Meuer S. C., Hussey R. E., Penta A. C., Fitzgerald K. A., Stadler B. M., Schlossman S. F., Reinherz E. L. Cellular origin of interleukin 2 (IL 2) in man: evidence for stimulus-restricted IL 2 production by T4+ and T8+ T lymphocytes. J Immunol. 1982 Sep;129(3):1076–1079. [PubMed] [Google Scholar]
  15. Muraguchi A., Butler J. L., Kehrl J. H., Fauci A. S. Differential sensitivity of human B cell subsets to activation signals delivered by anti-mu antibody and proliferative signals delivered by a monoclonal B cell growth factor. J Exp Med. 1983 Feb 1;157(2):530–546. doi: 10.1084/jem.157.2.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muraguchi A., Fauci A. S. Proliferative responses of normal human B lymphocytes. Development of an assay system for human B cell growth factor (BCGF). J Immunol. 1982 Sep;129(3):1104–1108. [PubMed] [Google Scholar]
  17. Murakawa Y., Takada S., Ueda Y., Suzuki N., Hoshino T., Sakane T. Characterization of T lymphocyte subpopulations responsible for deficient interleukin 2 activity in patients with systemic lupus erythematosus. J Immunol. 1985 Jan;134(1):187–195. [PubMed] [Google Scholar]
  18. Palacios R., Guy K., Van Heyningen V. Monoclonal antibodies against HLA-DR antigens acting on stimulator cells prevent OKT8+ T lymphocytes from acquiring sensitivity to interleukin 2 and expressing suppressor function. Eur J Immunol. 1983 Jan;13(1):64–72. doi: 10.1002/eji.1830130114. [DOI] [PubMed] [Google Scholar]
  19. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinherz E. L., Schlossman S. F. Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings. N Engl J Med. 1980 Aug 14;303(7):370–373. doi: 10.1056/NEJM198008143030704. [DOI] [PubMed] [Google Scholar]
  21. Robb R. J., Greene W. C. Direct demonstration of the identity of T cell growth factor binding protein and the Tac antigen. J Exp Med. 1983 Oct 1;158(4):1332–1337. doi: 10.1084/jem.158.4.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sakane T., Kotani H., Takada S., Murakawa Y., Ueda Y. A defect in the suppressor circuits among OKT4+ cell populations in patients with systemic lupus erythematosus occurs independently of a defect in the OKT8+ suppressor T cell function. J Immunol. 1983 Aug;131(2):753–761. [PubMed] [Google Scholar]
  23. Smolen J. S., Luger T. A., Chused T. M., Steinberg A. D. Responder cells in the human autologous mixed lymphocyte reaction. J Clin Invest. 1981 Dec;68(6):1601–1604. doi: 10.1172/JCI110416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Suzuki N., Sakane T., Ueda Y., Takada S., Murakawa Y., Tsunematsu T., Tsuchiya T., Niwa Y. [Studies of the mechanisms of human B cell activation. III. Development of an assay system for human B cell differentiation factors (BCDF) and identification of BCDF-producing T cell subsets]. Arerugi. 1984 Nov;33(11):963–969. [PubMed] [Google Scholar]
  25. Takada S., Ueda Y., Murakawa Y., Suzuki N., Sakane T. Functional heterogeneities among concanavalin A-activated OKT4+ and OKT8+ cells by using autologous erythrocyte rosette technique. J Clin Invest. 1983 Dec;72(6):2060–2071. doi: 10.1172/JCI111171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takada S., Ueda Y., Suzuki N., Murakawa Y., Hoshino T., Green I., Steinberg A. D., Horwitz D. A., Sakane T. Abnormalities in autologous mixed lymphocyte reaction-activated immunologic processes in systemic lupus erythematosus and their possible correction by interleukin 2. Eur J Immunol. 1985 Mar;15(3):262–267. doi: 10.1002/eji.1830150310. [DOI] [PubMed] [Google Scholar]
  27. Tsudo M., Uchiyama T., Uchino H. Expression of Tac antigen on activated normal human B cells. J Exp Med. 1984 Aug 1;160(2):612–617. doi: 10.1084/jem.160.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ueda Y., Sakane T., Suzuki N., Takada S., Murakawa Y., Tsunematsu T., Niwa Y., Tsuchiya T. [Studies of the mechanisms of human B cell activation. I. Development of an assay system for human B cell growth factors (BCGF) and identification of BCGF-producing T cell subsets]. Arerugi. 1984 Oct;33(10):859–867. [PubMed] [Google Scholar]
  29. Zubler R. H., Lowenthal J. W., Erard F., Hashimoto N., Devos R., MacDonald H. R. Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med. 1984 Oct 1;160(4):1170–1183. doi: 10.1084/jem.160.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES