Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 May;63(5):2079–2081. doi: 10.1128/iai.63.5.2079-2081.1995

Impact of antigen-presenting cells on cytokine profiles of human Th clones established after stimulation with Mycobacterium tuberculosis antigens.

P Conradt 1, S H Kaufmann 1
PMCID: PMC173268  PMID: 7729923

Abstract

Human T cells reactive with mycobacterial antigens are generally considered to correlate with a Th1 cytokine profile. Our data show that, in addition, Th0 and Th2 clones develop in bulk culture with appropriate antigen-presenting cells before cloning. CD4+ blasts activated by mycobacterial antigens were cloned, and their mRNA patterns for the interleukins (IL) IL-2, IL-4, IL-5, IL-6, and IL-10 and gamma interferon were characterized by reverse-transcribed PCR. Nonadherent, nonrosetting, enriched peripheral blood mononuclear cells promoted development of Th0; after further depletion of monocytes and natural killer cells, Th2 clones were also found. Epstein-Barr virus-transformed B cells, with specificity for the stimulating antigen, increased the proportion of Th2 clones.

Full Text

The Full Text of this article is available as a PDF (181.7 KB).

Selected References

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

  1. Barnes P. F., Abrams J. S., Lu S., Sieling P. A., Rea T. H., Modlin R. L. Patterns of cytokine production by mycobacterium-reactive human T-cell clones. Infect Immun. 1993 Jan;61(1):197–203. doi: 10.1128/iai.61.1.197-203.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. F., Chatterjee D., Abrams J. S., Lu S., Wang E., Yamamura M., Brennan P. J., Modlin R. L. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J Immunol. 1992 Jul 15;149(2):541–547. [PubMed] [Google Scholar]
  3. Boom W. H., Wallis R. S., Chervenak K. A. Human Mycobacterium tuberculosis-reactive CD4+ T-cell clones: heterogeneity in antigen recognition, cytokine production, and cytotoxicity for mononuclear phagocytes. Infect Immun. 1991 Aug;59(8):2737–2743. doi: 10.1128/iai.59.8.2737-2743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burdin N., Péronne C., Banchereau J., Rousset F. Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med. 1993 Feb 1;177(2):295–304. doi: 10.1084/jem.177.2.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. D'Andrea A., Rengaraju M., Valiante N. M., Chehimi J., Kubin M., Aste M., Chan S. H., Kobayashi M., Young D., Nickbarg E. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med. 1992 Nov 1;176(5):1387–1398. doi: 10.1084/jem.176.5.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Del Prete G., De Carli M., Almerigogna F., Giudizi M. G., Biagiotti R., Romagnani S. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol. 1993 Jan 15;150(2):353–360. [PubMed] [Google Scholar]
  9. Ehlers S., Smith K. A. Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med. 1991 Jan 1;173(1):25–36. doi: 10.1084/jem.173.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haanen J. B., de Waal Malefijt R., Res P. C., Kraakman E. M., Ottenhoff T. H., de Vries R. R., Spits H. Selection of a human T helper type 1-like T cell subset by mycobacteria. J Exp Med. 1991 Sep 1;174(3):583–592. doi: 10.1084/jem.174.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  13. Lanzavecchia A., Parodi B., Celada F. Activation of human B lymphocytes: frequency of antigen-specific B cells triggered by alloreactive or by antigen-specific T cell clones. Eur J Immunol. 1983 Sep;13(9):733–738. doi: 10.1002/eji.1830130908. [DOI] [PubMed] [Google Scholar]
  14. Maggi E., Parronchi P., Manetti R., Simonelli C., Piccinni M. P., Rugiu F. S., De Carli M., Ricci M., Romagnani S. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992 Apr 1;148(7):2142–2147. [PubMed] [Google Scholar]
  15. Magilavy D. B., Fitch F. W., Gajewski T. F. Murine hepatic accessory cells support the proliferation of Th1 but not Th2 helper T lymphocyte clones. J Exp Med. 1989 Sep 1;170(3):985–990. doi: 10.1084/jem.170.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Manetti R., Gerosa F., Giudizi M. G., Biagiotti R., Parronchi P., Piccinni M. P., Sampognaro S., Maggi E., Romagnani S., Trinchieri G. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med. 1994 Apr 1;179(4):1273–1283. doi: 10.1084/jem.179.4.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
  19. 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]
  20. Parronchi P., Macchia D., Piccinni M. P., Biswas P., Simonelli C., Maggi E., Ricci M., Ansari A. A., Romagnani S. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4538–4542. doi: 10.1073/pnas.88.10.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol. 1994;12:227–257. doi: 10.1146/annurev.iy.12.040194.001303. [DOI] [PubMed] [Google Scholar]
  22. Rotteveel F. T., Kokkelink I., van Lier R. A., Kuenen B., Meager A., Miedema F., Lucas C. J. Clonal analysis of functionally distinct human CD4+ T cell subsets. J Exp Med. 1988 Nov 1;168(5):1659–1673. doi: 10.1084/jem.168.5.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sieling P. A., Abrams J. S., Yamamura M., Salgame P., Bloom B. R., Rea T. H., Modlin R. L. Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy. J Immunol. 1993 Jun 15;150(12):5501–5510. [PubMed] [Google Scholar]
  24. Surcel H. M., Troye-Blomberg M., Paulie S., Andersson G., Moreno C., Pasvol G., Ivanyi J. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. Immunology. 1994 Feb;81(2):171–176. [PMC free article] [PubMed] [Google Scholar]
  25. Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
  26. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  27. Yssel H., De Waal Malefyt R., Roncarolo M. G., Abrams J. S., Lahesmaa R., Spits H., de Vries J. E. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol. 1992 Oct 1;149(7):2378–2384. [PubMed] [Google Scholar]
  28. Yssel H., Fasler S., de Vries J. E., de Waal Malefyt R. IL-12 transiently induces IFN-gamma transcription and protein synthesis in human CD4+ allergen-specific Th2 T cell clones. Int Immunol. 1994 Jul;6(7):1091–1096. doi: 10.1093/intimm/6.7.1091. [DOI] [PubMed] [Google Scholar]
  29. de Waal Malefyt R., Yssel H., de Vries J. E. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol. 1993 Jun 1;150(11):4754–4765. [PubMed] [Google Scholar]
  30. elGhazali G. E., Paulie S., Andersson G., Hansson Y., Holmquist G., Sun J. B., Olsson T., Ekre H. P., Troye-Blomberg M. Number of interleukin-4- and interferon-gamma-secreting human T cells reactive with tetanus toxoid and the mycobacterial antigen PPD or phytohemagglutinin: distinct response profiles depending on the type of antigen used for activation. Eur J Immunol. 1993 Nov;23(11):2740–2745. doi: 10.1002/eji.1830231103. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES