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. 1996 Oct 1;184(4):1507–1512. doi: 10.1084/jem.184.4.1507

Beta 2-microglobulin-dependent T cells are dispensable for allergen- induced T helper 2 responses

PMCID: PMC2192811  PMID: 8879221

Abstract

CD4+ and CD8+ alpha/beta+ T cells of the T helper cell (Th)2 phenotype produce the cytokines IL-4, IL-5, and IL-13 that promote IgE production and eosinophilic inflammation. IL-4 may play an important role in mediating the differentiation of antigenically naive alpha/beta+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or CD4-CD8-) alpha/beta+ T cells comprise a beta 2-microglobulin (beta 2m)-dependent cell population that rapidly produces IL-4 after cell activation in vitro and in vivo and has been proposed as a source of IL-4 for Th2 cell differentiation. alpha/beta+ CD8+ T cells, most of which require beta 2m for their development, have also been proposed as positive regulators of allergen-induced Th2 responses. We tested whether beta 2m- dependent T cells were essential for Th2 cell-mediated allergic reactions by treating wild-type, beta 2m-deficient (beta 2m -/-), and IL-4-deficient (IL-4 -/-) mice of the C57BL/6 genetic background with ovalbumin (OVA), using a protocol that induces robust allergic pulmonary disease in wild-type mice. OVA-treated beta 2m -/- mice had circulating levels of total and OVA-specific IgE, pulmonary eosinophilia, and expression of IL-4, IL-5, and IL-13 mRNA in bronchial lymph node tissue similar to that of OVA-treated wild-type mice. In contrast, these responses in OVA-treated IL-4 -/- mice were all either undetectable or markedly reduced compared with wild-type mice, confirming that IL-4 was required in this allergic model. These results indicate that the NK1.1+ alpha/beta+ T cell population, as well as other beta 2m-dependent populations, such as most peripheral alpha/beta+ CD8+ T cells, are dispensable for the Th2 pulmonary response to protein allergens.

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Selected References

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  1. Aoki I., Kinzer C., Shirai A., Paul W. E., Klinman D. M. IgE receptor-positive non-B/non-T cells dominate the production of interleukin 4 and interleukin 6 in immunized mice. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2534–2538. doi: 10.1073/pnas.92.7.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bendelac A., Killeen N., Littman D. R., Schwartz R. H. A subset of CD4+ thymocytes selected by MHC class I molecules. Science. 1994 Mar 25;263(5154):1774–1778. doi: 10.1126/science.7907820. [DOI] [PubMed] [Google Scholar]
  3. Brusselle G. G., Kips J. C., Tavernier J. H., van der Heyden J. G., Cuvelier C. A., Pauwels R. A., Bluethmann H. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy. 1994 Jan;24(1):73–80. doi: 10.1111/j.1365-2222.1994.tb00920.x. [DOI] [PubMed] [Google Scholar]
  4. Correa I., Bix M., Liao N. S., Zijlstra M., Jaenisch R., Raulet D. Most gamma delta T cells develop normally in beta 2-microglobulin-deficient mice. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):653–657. doi: 10.1073/pnas.89.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corry D. B., Folkesson H. G., Warnock M. L., Erle D. J., Matthay M. A., Wiener-Kronish J. P., Locksley R. M. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med. 1996 Jan 1;183(1):109–117. doi: 10.1084/jem.183.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coyle A. J., Erard F., Bertrand C., Walti S., Pircher H., Le Gros G. Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia. J Exp Med. 1995 Mar 1;181(3):1229–1233. doi: 10.1084/jem.181.3.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Finkelman F. D., Goroff D. K., Fultz M., Morris S. C., Holmes J. M., Mond J. J. Polyclonal activation of the murine immune system by an antibody to IgD. X. Evidence that the precursors of IgG1-secreting cells are newly generated membrane IgD+B cells rather than the B cells that are initially activated by anti-IgD antibody. J Immunol. 1990 Dec 1;145(11):3562–3569. [PubMed] [Google Scholar]
  8. Foster P. S., Hogan S. P., Ramsay A. J., Matthaei K. I., Young I. G. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996 Jan 1;183(1):195–201. doi: 10.1084/jem.183.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gross A., Ben-Sasson S. Z., Paul W. E. Anti-IL-4 diminishes in vivo priming for antigen-specific IL-4 production by T cells. J Immunol. 1993 Mar 15;150(6):2112–2120. [PubMed] [Google Scholar]
  10. Guery J. C., Galbiati F., Smiroldo S., Adorini L. Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)-microglobulin-deficient BALB/c mice. J Exp Med. 1996 Feb 1;183(2):485–497. doi: 10.1084/jem.183.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamelmann E., Oshiba A., Paluh J., Bradley K., Loader J., Potter T. A., Larsen G. L., Gelfand E. W. Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization. J Exp Med. 1996 Apr 1;183(4):1719–1729. doi: 10.1084/jem.183.4.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holt P. G. Macrophage: dendritic cell interaction in regulation of the IgE response in asthma. Clin Exp Allergy. 1993 Jan;23(1):4–6. doi: 10.1111/j.1365-2222.1993.tb02476.x. [DOI] [PubMed] [Google Scholar]
  13. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  14. Kopf M., Brombacher F., Hodgkin P. D., Ramsay A. J., Milbourne E. A., Dai W. J., Ovington K. S., Behm C. A., Köhler G., Young I. G. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity. 1996 Jan;4(1):15–24. doi: 10.1016/s1074-7613(00)80294-0. [DOI] [PubMed] [Google Scholar]
  15. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  16. Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
  17. Lewis D. B., Prickett K. S., Larsen A., Grabstein K., Weaver M., Wilson C. B. Restricted production of interleukin 4 by activated human T cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9743–9747. doi: 10.1073/pnas.85.24.9743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mosmann T. R. Cytokines, differentiation and functions of subsets of CD4 and CD8 T cells. Behring Inst Mitt. 1995 Jun;(96):1–6. [PubMed] [Google Scholar]
  19. Mu H. H., Sewell W. A. Regulation of DTH and IgE responses by IL-4 and IFN-gamma in immunized mice given pertussis toxin. Immunology. 1994 Dec;83(4):639–645. [PMC free article] [PubMed] [Google Scholar]
  20. O'Garra A., Murphy K. Role of cytokines in determining T-lymphocyte function. Curr Opin Immunol. 1994 Jun;6(3):458–466. doi: 10.1016/0952-7915(94)90128-7. [DOI] [PubMed] [Google Scholar]
  21. Reiner S. L., Seder R. A. T helper cell differentiation in immune response. Curr Opin Immunol. 1995 Jun;7(3):360–366. doi: 10.1016/0952-7915(95)80111-1. [DOI] [PubMed] [Google Scholar]
  22. Reiner S. L., Zheng S., Corry D. B., Locksley R. M. Constructing polycompetitor cDNAs for quantitative PCR. J Immunol Methods. 1993 Sep 27;165(1):37–46. doi: 10.1016/0022-1759(93)90104-f. [DOI] [PubMed] [Google Scholar]
  23. Romagnani S. Atopic allergy and other hypersensitivities editorial overview: technological advances and new insights into pathogenesis prelude novel therapeutic strategies. Curr Opin Immunol. 1995 Dec;7(6):745–750. doi: 10.1016/0952-7915(95)80042-5. [DOI] [PubMed] [Google Scholar]
  24. Vicari A. P., Mocci S., Openshaw P., O'Garra A., Zlotnik A. Mouse gamma delta TCR+NK1.1+ thymocytes specifically produce interleukin-4, are major histocompatibility complex class I independent, and are developmentally related to alpha beta TCR+NK1.1+ thymocytes. Eur J Immunol. 1996 Jul;26(7):1424–1429. doi: 10.1002/eji.1830260704. [DOI] [PubMed] [Google Scholar]
  25. Vicari A. P., Zlotnik A. Mouse NK1.1+ T cells: a new family of T cells. Immunol Today. 1996 Feb;17(2):71–76. doi: 10.1016/0167-5699(96)80582-2. [DOI] [PubMed] [Google Scholar]
  26. Yoshimoto T., Bendelac A., Watson C., Hu-Li J., Paul W. E. Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production. Science. 1995 Dec 15;270(5243):1845–1847. doi: 10.1126/science.270.5243.1845. [DOI] [PubMed] [Google Scholar]
  27. Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. von der Weid T., Kopf M., Köhler G., Langhorne J. The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice. Eur J Immunol. 1994 Oct;24(10):2285–2293. doi: 10.1002/eji.1830241004. [DOI] [PubMed] [Google Scholar]

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