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. 1982 Oct 1;156(4):1250–1255. doi: 10.1084/jem.156.4.1250

Tumor-promoting phorbol esters selectively abrogate the expression of the T4 differentiation antigen expressed on normal and malignant (Sezary) T helper lymphocytes

PMCID: PMC2186807  PMID: 6218216

Abstract

12-O-tetradecanoylphorbol-13-acetate (TPA) selectively abrogates, in nanomolar concentrations, the expression of the T4 differentiation antigen, as defined by the monoclonal anti-T4 antibody (1) on Il-2- producing T helper lymphocytes from normal donors and on T helper lymphocytes from a patient with malignant T cell lymphoma (Sezary's syndrome); this compound does not affect the expression of cell surface antigens as defined by the antibodies anti-OKT3, -T6, -T8, -T11, Ia, or anti-surface immunoglobulin. Abrogation of the T4 antigen expression is concentration dependent, completed within 8 h of incubation at 37 degrees C, does not occur at 4 degrees C, and is reversible. Only those phorbol-esters known to have tumor-promoting activity in vivo (2) affect the T4 antigen, whereas nonpromoting compounds are ineffective.

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Selected References

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

  1. Abb J., Bayliss G. J., Deinhardt F. Lymphocyte activation by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). J Immunol. 1979 May;122(5):1639–1642. [PubMed] [Google Scholar]
  2. Diamond L., O'Brien T. G., Baird W. M. Tumor promoters and the mechanism of tumor promotion. Adv Cancer Res. 1980;32:1–74. doi: 10.1016/s0065-230x(08)60360-7. [DOI] [PubMed] [Google Scholar]
  3. Farrar J. J., Benjamin W. R., Hilfiker M. L., Howard M., Farrar W. L., Fuller-Farrar J. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–166. doi: 10.1111/j.1600-065x.1982.tb00414.x. [DOI] [PubMed] [Google Scholar]
  4. Fröland S., Natvig J. B., Berdal P. Surface-bound immunoglobulin as a marker of B lymphocytes in man. Nat New Biol. 1971 Dec 22;234(51):251–252. doi: 10.1038/newbio234251a0. [DOI] [PubMed] [Google Scholar]
  5. Koretzky G. A., Daniele R. P., Nowell P. C. A phorbol ester (TPA) can replace macrophages in human lymphocyte cultures stimulated with a mitogen but not with an antigen. J Immunol. 1982 Apr;128(4):1776–1780. [PubMed] [Google Scholar]
  6. Nagasawa K., Mak T. W. Phorbol esters induce differentiation in human malignant T lymphoblasts. Proc Natl Acad Sci U S A. 1980 May;77(5):2964–2968. doi: 10.1073/pnas.77.5.2964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  9. Sando J. J., Hilfiker M. L., Salomon D. S., Farrar J. J. Specific receptors for phorbol esters in lymphoid cell populations: role in enhanced production of T-cell growth factor. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1189–1193. doi: 10.1073/pnas.78.2.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
  11. Terhorst C., van Agthoven A., LeClair K., Snow P., Reinherz E., Schlossman S. Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. Cell. 1981 Mar;23(3):771–780. doi: 10.1016/0092-8674(81)90441-4. [DOI] [PubMed] [Google Scholar]
  12. Thomas Y., Sosman J., Rogozinski L., Irigoyen O., Kung P. C., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. III. Regulation of helper factor production by T cell subsets. J Immunol. 1981 May;126(5):1948–1951. [PubMed] [Google Scholar]
  13. Touraine J. L., Hadden J. W., Touraine F., Hadden E. M., Estensen R., Good R. A. Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation. J Exp Med. 1977 Feb 1;145(2):460–465. doi: 10.1084/jem.145.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Verbi W., Greaves M. F., Schneider C., Koubek K., Janossy G., Stein H., Kung P., Goldstein G. Monoclonal antibodies OKT 11 and OKT 11A have pan-T reactivity and block sheep erythrocyte "receptors". Eur J Immunol. 1982 Jan;12(1):81–86. doi: 10.1002/eji.1830120115. [DOI] [PubMed] [Google Scholar]

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