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. 1995 Jun 6;92(12):5501–5505. doi: 10.1073/pnas.92.12.5501

Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

R J Capocasale 1, R J Lamb 1, E C Vonderheid 1, F E Fox 1, A H Rook 1, P C Nowell 1, J S Moore 1
PMCID: PMC41723  PMID: 7777538

Abstract

Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease.

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Selected References

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

  1. Edelson R. L. Cutaneous T cell lymphoma: mycosis fungoides, Sézary syndrome, and other variants. J Am Acad Dermatol. 1980 Feb;2(2):89–106. doi: 10.1016/s0190-9622(80)80385-9. [DOI] [PubMed] [Google Scholar]
  2. Ellingsworth L., Nakayama D., Dasch J., Segarini P., Carrillo P., Waegell W. Transforming growth factor beta 1 (TGF-beta 1) receptor expression on resting and mitogen-activated T cells. J Cell Biochem. 1989 Apr;39(4):489–500. doi: 10.1002/jcb.240390414. [DOI] [PubMed] [Google Scholar]
  3. Fox F. E., Capocasale R. J., Ford H. C., Lamb R. J., Moore J. S., Nowell P. C. Transforming growth factor-beta inhibits human T-cell proliferation through multiple targets. Lymphokine Cytokine Res. 1992 Dec;11(6):299–305. [PubMed] [Google Scholar]
  4. Ghosh S. K., Abrams J. T., Terunuma H., Vonderheid E. C., DeFreitas E. Human T-cell leukemia virus type I tax/rex DNA and RNA in cutaneous T-cell lymphoma. Blood. 1994 Oct 15;84(8):2663–2671. [PubMed] [Google Scholar]
  5. Heald P., Yan S. L., Edelson R. Profound deficiency in normal circulating T cells in erythrodermic cutaneous T-cell lymphoma. Arch Dermatol. 1994 Feb;130(2):198–203. [PubMed] [Google Scholar]
  6. Israels L. G., Israels S. J., Begleiter A., Verburg L., Schwartz L., Mowat M. R., Johnston J. B. Role of transforming growth factor-beta in chronic lymphocytic leukemia. Leuk Res. 1993 Jan;17(1):81–87. doi: 10.1016/0145-2126(93)90144-a. [DOI] [PubMed] [Google Scholar]
  7. Joly M., Kazlauskas A., Fay F. S., Corvera S. Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites. Science. 1994 Feb 4;263(5147):684–687. doi: 10.1126/science.8303278. [DOI] [PubMed] [Google Scholar]
  8. Kadin M. E., Cavaille-Coll M. W., Gertz R., Massagué J., Cheifetz S., George D. Loss of receptors for transforming growth factor beta in human T-cell malignancies. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6002–6006. doi: 10.1073/pnas.91.13.6002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kehrl J. H., Roberts A. B., Wakefield L. M., Jakowlew S., Sporn M. B., Fauci A. S. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986 Dec 15;137(12):3855–3860. [PubMed] [Google Scholar]
  10. Kehrl J. H., Wakefield L. M., Roberts A. B., Jakowlew S., Alvarez-Mon M., Derynck R., Sporn M. B., Fauci A. S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. doi: 10.1084/jem.163.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kerbel R. S. Expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer. Malignant melanoma as a paradigm. Am J Pathol. 1992 Sep;141(3):519–524. [PMC free article] [PubMed] [Google Scholar]
  12. Lin H. Y., Wang X. F., Ng-Eaton E., Weinberg R. A., Lodish H. F. Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. Cell. 1992 Feb 21;68(4):775–785. doi: 10.1016/0092-8674(92)90152-3. [DOI] [PubMed] [Google Scholar]
  13. López-Casillas F., Wrana J. L., Massagué J. Betaglycan presents ligand to the TGF beta signaling receptor. Cell. 1993 Jul 2;73(7):1435–1444. doi: 10.1016/0092-8674(93)90368-z. [DOI] [PubMed] [Google Scholar]
  14. Massagué J., Cheifetz S., Boyd F. T., Andres J. L. TGF-beta receptors and TGF-beta binding proteoglycans: recent progress in identifying their functional properties. Ann N Y Acad Sci. 1990;593:59–72. doi: 10.1111/j.1749-6632.1990.tb16100.x. [DOI] [PubMed] [Google Scholar]
  15. Massagué J. Receptors for the TGF-beta family. Cell. 1992 Jun 26;69(7):1067–1070. doi: 10.1016/0092-8674(92)90627-o. [DOI] [PubMed] [Google Scholar]
  16. Miyazono K., Olofsson A., Colosetti P., Heldin C. H. A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 1991 May;10(5):1091–1101. doi: 10.1002/j.1460-2075.1991.tb08049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nowell P. C., Vonderheid E. C., Besa E., Hoxie J. A., Moreau L., Finan J. B. The most common chromosome change in 86 chronic B cell or T cell tumors: a 14q32 translocation. Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):219–227. doi: 10.1016/0165-4608(86)90050-6. [DOI] [PubMed] [Google Scholar]
  18. Rook A. H., Vowels B. R., Jaworsky C., Singh A., Lessin S. R. The immunopathogenesis of cutaneous T-cell lymphoma. Abnormal cytokine production by Sézary T cells. Arch Dermatol. 1993 Apr;129(4):486–489. [PubMed] [Google Scholar]
  19. Sterry W., Mielke V. CD4+ cutaneous T-cell lymphomas show the phenotype of helper/inducer T cells (CD45RA-, CDw29+). J Invest Dermatol. 1989 Sep;93(3):413–416. [PubMed] [Google Scholar]
  20. Vowels B. R., Cassin M., Vonderheid E. C., Rook A. H. Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells. J Invest Dermatol. 1992 Jul;99(1):90–94. doi: 10.1111/1523-1747.ep12611877. [DOI] [PubMed] [Google Scholar]
  21. Wahl S. M., Hunt D. A., Wong H. L., Dougherty S., McCartney-Francis N., Wahl L. M., Ellingsworth L., Schmidt J. A., Hall G., Roberts A. B. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol. 1988 May 1;140(9):3026–3032. [PubMed] [Google Scholar]
  22. Wood G. S., Hong S. R., Sasaki D. T., Abel E. A., Hoppe R. T., Warnke R. A., Morhenn V. B. Leu-8/CD7 antigen expression by CD3+ T cells: comparative analysis of skin and blood in mycosis fungoides/Sézary syndrome relative to normal blood values. J Am Acad Dermatol. 1990 Apr;22(4):602–607. doi: 10.1016/0190-9622(90)70080-2. [DOI] [PubMed] [Google Scholar]
  23. Zucker-Franklin D., Coutavas E. E., Rush M. G., Zouzias D. C. Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7630–7634. doi: 10.1073/pnas.88.17.7630. [DOI] [PMC free article] [PubMed] [Google Scholar]

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