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. 1995 Dec 1;182(6):1655–1661. doi: 10.1084/jem.182.6.1655

CD30-mediated signaling promotes the development of human T helper type 2-like T cells

PMCID: PMC2192264  PMID: 7500010

Abstract

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti- CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag- specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.

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Selected References

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  1. Alzona M., Jäck H. M., Fisher R. I., Ellis T. M. CD30 defines a subset of activated human T cells that produce IFN-gamma and IL-5 and exhibit enhanced B cell helper activity. J Immunol. 1994 Oct 1;153(7):2861–2867. [PubMed] [Google Scholar]
  2. Alzona M., Jäck H. M., Fisher R. I., Ellis T. M. IL-12 activates IFN-gamma production through the preferential activation of CD30+ T cells. J Immunol. 1995 Jan 1;154(1):9–16. [PubMed] [Google Scholar]
  3. Andreesen R., Osterholz J., Löhr G. W., Bross K. J. A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts. Blood. 1984 Jun;63(6):1299–1302. [PubMed] [Google Scholar]
  4. Corry D. B., Reiner S. L., Linsley P. S., Locksley R. M. Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis. J Immunol. 1994 Nov 1;153(9):4142–4148. [PubMed] [Google Scholar]
  5. Del Prete G. F., De Carli M., Mastromauro C., Biagiotti R., Macchia D., Falagiani P., Ricci M., Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991 Jul;88(1):346–350. doi: 10.1172/JCI115300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Del Prete G., De Carli M., Almerigogna F., Daniel C. K., D'Elios M. M., Zancuoghi G., Vinante F., Pizzolo G., Romagnani S. Preferential expression of CD30 by human CD4+ T cells producing Th2-type cytokines. FASEB J. 1995 Jan;9(1):81–86. [PubMed] [Google Scholar]
  7. Del Prete G., Maggi E., Pizzolo G., Romagnani S. CD30, Th2 cytokines and HIV infection: a complex and fascinating link. Immunol Today. 1995 Feb;16(2):76–80. doi: 10.1016/0167-5699(95)80092-1. [DOI] [PubMed] [Google Scholar]
  8. Ellis T. M., Simms P. E., Slivnick D. J., Jäck H. M., Fisher R. I. CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. J Immunol. 1993 Sep 1;151(5):2380–2389. [PubMed] [Google Scholar]
  9. Gajewski T. F., Lancki D. W., Stack R., Fitch F. W. "Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype. J Exp Med. 1994 Feb 1;179(2):481–491. doi: 10.1084/jem.179.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gruss H. J., Boiani N., Williams D. E., Armitage R. J., Smith C. A., Goodwin R. G. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. Blood. 1994 Apr 15;83(8):2045–2056. [PubMed] [Google Scholar]
  11. Harding F. A., McArthur J. G., Gross J. A., Raulet D. H., Allison J. P. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. doi: 10.1038/356607a0. [DOI] [PubMed] [Google Scholar]
  12. Hsieh C. S., Heimberger A. B., Gold J. S., O'Garra A., Murphy K. M. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6065–6069. doi: 10.1073/pnas.89.13.6065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  14. Jenkins M. K., Chen C. A., Jung G., Mueller D. L., Schwartz R. H. Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody. J Immunol. 1990 Jan 1;144(1):16–22. [PubMed] [Google Scholar]
  15. Josimovic-Alasevic O., Dürkop H., Schwarting R., Backé E., Stein H., Diamantstein T. Ki-1 (CD30) antigen is released by Ki-1-positive tumor cells in vitro and in vivo. I. Partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture supernatants and in serum by an enzyme-linked immunosorbent assay. Eur J Immunol. 1989 Jan;19(1):157–162. doi: 10.1002/eji.1830190125. [DOI] [PubMed] [Google Scholar]
  16. Kurt-Jones E. A., Hamberg S., Ohara J., Paul W. E., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. doi: 10.1084/jem.166.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Manetti R., Annunziato F., Biagiotti R., Giudizi M. G., Piccinni M. P., Giannarini L., Sampognaro S., Parronchi P., Vinante F., Pizzolo G. CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection. J Exp Med. 1994 Dec 1;180(6):2407–2411. doi: 10.1084/jem.180.6.2407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Manetti R., Parronchi P., Giudizi M. G., Piccinni M. P., Maggi E., Trinchieri G., Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 1993 Apr 1;177(4):1199–1204. doi: 10.1084/jem.177.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  20. Nawrocki J. F., Kirsten E. S., Fisher R. I. Biochemical and structural properties of a Hodgkin's disease-related membrane protein. J Immunol. 1988 Jul 15;141(2):672–680. [PubMed] [Google Scholar]
  21. Parronchi P., De Carli M., Manetti R., Simonelli C., Sampognaro S., Piccinni M. P., Macchia D., Maggi E., Del Prete G., Romagnani S. IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol. 1992 Nov 1;149(9):2977–2983. [PubMed] [Google Scholar]
  22. Reiser H., Freeman G. J., Razi-Wolf Z., Gimmi C. D., Benacerraf B., Nadler L. M. Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):271–275. doi: 10.1073/pnas.89.1.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  24. Schwab U., Stein H., Gerdes J., Lemke H., Kirchner H., Schaadt M., Diehl V. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature. 1982 Sep 2;299(5878):65–67. doi: 10.1038/299065a0. [DOI] [PubMed] [Google Scholar]
  25. Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
  26. Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
  27. Smith C. A., Gruss H. J., Davis T., Anderson D., Farrah T., Baker E., Sutherland G. R., Brannan C. I., Copeland N. G., Jenkins N. A. CD30 antigen, a marker for Hodgkin's lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF. Cell. 1993 Jul 2;73(7):1349–1360. doi: 10.1016/0092-8674(93)90361-s. [DOI] [PubMed] [Google Scholar]
  28. Stein H., Mason D. Y., Gerdes J., O'Connor N., Wainscoat J., Pallesen G., Gatter K., Falini B., Delsol G., Lemke H. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985 Oct;66(4):848–858. [PubMed] [Google Scholar]
  29. Street N. E., Schumacher J. H., Fong T. A., Bass H., Fiorentino D. F., Leverah J. A., Mosmann T. R. Heterogeneity of mouse helper T cells. Evidence from bulk cultures and limiting dilution cloning for precursors of Th1 and Th2 cells. J Immunol. 1990 Mar 1;144(5):1629–1639. [PubMed] [Google Scholar]
  30. Tan P., Anasetti C., Hansen J. A., Melrose J., Brunvand M., Bradshaw J., Ledbetter J. A., Linsley P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993 Jan 1;177(1):165–173. doi: 10.1084/jem.177.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weaver C. T., Hawrylowicz C. M., Unanue E. R. T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8181–8185. doi: 10.1073/pnas.85.21.8181. [DOI] [PMC free article] [PubMed] [Google Scholar]

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