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. 1988 Sep;85(17):6478–6482. doi: 10.1073/pnas.85.17.6478

Blockade of the interleukin-2 receptor by anti-Tac antibody inhibits the generation of antigen-nonspecific suppressor T cells in vitro.

T Oh-Ishi 1, C K Goldman 1, J Misiti 1, T A Waldmann 1
PMCID: PMC281996  PMID: 2970641

Abstract

The role of interleukin 2 (IL-2) in the activation of suppressor T cells was investigated by using the monoclonal antibody anti-Tac, which blocks the binding of IL-2 to the 55-kDa peptide of the high-affinity IL-2 receptor. Anti-Tac was added to an antigen-nonspecific suppressor system in which Con A-induced suppressor T cells were generated during a preculture period, and their effects on immunoglobulin production were assessed in second, indicator cultures containing pokeweed mitogen and peripheral blood mononuclear cells. Anti-Tac added during the preculture period inhibited Con A-induced suppressor T-cell generation. Cells activated by a short (2-day) preculture period to become effectors of suppression were primarily of the Tac-positive, T8 (CD8)-positive phenotype. Tac-positive, T8-negative T cells might also contribute to the suppressor activity. Our studies indicate that anti-Tac, by producing a functional blockade of human high-affinity IL-2 receptors, inhibits the generation of antigen-nonspecific suppressor T cells.

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Selected References

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

  1. Depper J. M., Leonard W. J., Robb R. J., Waldmann T. A., Greene W. C. Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation. J Immunol. 1983 Aug;131(2):690–696. [PubMed] [Google Scholar]
  2. FitzGerald D. J., Waldmann T. A., Willingham M. C., Pastan I. Pseudomonas exotoxin-anti-TAC. Cell-specific immunotoxin active against cells expressing the human T cell growth factor receptor. J Clin Invest. 1984 Sep;74(3):966–971. doi: 10.1172/JCI111516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hedrick S. M., Germain R. N., Bevan M. J., Dorf M., Engel I., Fink P., Gascoigne N., Heber-Katz E., Kapp J., Kaufmann Y. Rearrangement and transcription of a T-cell receptor beta-chain gene in different T-cell subsets. Proc Natl Acad Sci U S A. 1985 Jan;82(2):531–535. doi: 10.1073/pnas.82.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kronenberg M., Goverman J., Haars R., Malissen M., Kraig E., Phillips L., Delovitch T., Suciu-Foca N., Hood L. Rearrangement and transcription of the beta-chain genes of the T-cell antigen receptor in different types of murine lymphocytes. Nature. 1985 Feb 21;313(6004):647–653. doi: 10.1038/313647a0. [DOI] [PubMed] [Google Scholar]
  5. Kupiec-Weglinski J. W., Diamantstein T., Tilney N. L., Strom T. B. Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2624–2627. doi: 10.1073/pnas.83.8.2624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lawrence E. C., Blaese R. M., Martin R. R., Stevens P. M. Immunoglobulin secreting cells in normal human bronchial lavage fluids. J Clin Invest. 1978 Oct;62(4):832–835. doi: 10.1172/JCI109195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Leonard W. J., Depper J. M., Robb R. J., Waldmann T. A., Greene W. C. Characterization of the human receptor for T-cell growth factor. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6957–6961. doi: 10.1073/pnas.80.22.6957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ortaldo J. R., Mason A. T., Gerard J. P., Henderson L. E., Farrar W., Hopkins R. F., 3rd, Herberman R. B., Rabin H. Effects of natural and recombinant IL 2 on regulation of IFN gamma production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol. 1984 Aug;133(2):779–783. [PubMed] [Google Scholar]
  12. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schneider T. M., Kupiec-Weglinski J. W., Towpik E., Padberg W., Araneda D., Diamantstein T., Strom T. B., Tilney N. L. Development of suppressor lymphocytes during acute rejection of rat cardiac allografts and preservation of suppression by anti-IL-2-receptor monoclonal antibody. Transplantation. 1986 Aug;42(2):191–196. doi: 10.1097/00007890-198608000-00017. [DOI] [PubMed] [Google Scholar]
  14. Shapiro M. E., Kirkman R. L., Reed M. H., Puskas J. D., Mazoujian G., Letvin N. L., Carpenter C. B., Milford E. L., Waldmann T. A., Strom T. B. Monoclonal anti-IL-2 receptor antibody in primate renal transplantation. Transplant Proc. 1987 Feb;19(1 Pt 1):594–598. [PubMed] [Google Scholar]
  15. Sharon M., Klausner R. D., Cullen B. R., Chizzonite R., Leonard W. J. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. doi: 10.1126/science.3095922. [DOI] [PubMed] [Google Scholar]
  16. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  17. Tsudo M., Goldman C. K., Bongiovanni K. F., Chan W. C., Winton E. F., Yagita M., Grimm E. A., Waldmann T. A. The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394–5398. doi: 10.1073/pnas.84.15.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. doi: 10.1073/pnas.83.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tsudo M., Uchiyama T., Takatsuki K., Uchino H., Yodoi J. Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody. J Immunol. 1982 Aug;129(2):592–595. [PubMed] [Google Scholar]
  20. 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]
  21. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  22. Uchiyama T., Nelson D. L., Fleisher T. A., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J Immunol. 1981 Apr;126(4):1398–1403. [PubMed] [Google Scholar]
  23. Waldmann T. A., Goldman C. K., Robb R. J., Depper J. M., Leonard W. J., Sharrow S. O., Bongiovanni K. F., Korsmeyer S. J., Greene W. C. Expression of interleukin 2 receptors on activated human B cells. J Exp Med. 1984 Nov 1;160(5):1450–1466. doi: 10.1084/jem.160.5.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Waldmann T. A. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986 May 9;232(4751):727–732. doi: 10.1126/science.3008337. [DOI] [PubMed] [Google Scholar]
  25. Zoumbos N. C., Gascón P., Djeu J. Y., Trost S. R., Young N. S. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257–265. doi: 10.1056/NEJM198501313120501. [DOI] [PubMed] [Google Scholar]

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