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Mol Med. 1995 November; 1(7): 821–826.
PMCID: PMC2230008

Local expansion of allergen-specific CD30+Th2-type gamma delta T cells in bronchial asthma.


BACKGROUND: T lymphocytes infiltrating airways during the allergic immune response play a fundamental role in recruiting other specialized cells, such as eosinophils, by secreting interleukin 5 (IL-5), and promoting local and systemic IgE synthesis by producing IL-4. Whether these presumed allergen-specific T cells are of mucosal or systemic origin is still a matter of conjecture. MATERIALS AND METHODS: Immunophenotype, IL-4 production, and in vitro proliferative response to specific or unrelated allergens were analyzed in the bronchoalveolar lavage (BAL) fluid lymphocyte suspensions obtained from untreated patients with allergic asthma. Healthy subjects and patients affected by pulmonary sarcoidosis, a granulomatous lung disease characterized by infiltrating Th1 CD4+ lymphocytes, served as controls. RESULTS: The proportions of gamma delta T lymphocytes, mostly CD4+ or CD4- (-)CD8-, was higher in asthmatic subjects than in controls (p < 0.05). Most BAL gamma delta CD4+ lymphocytes of asthmatic patients displayed the T cell receptor (TCR)-gamma delta V delta 1 chain. While CD30 antigen coexpression on the surface of BAL alpha beta(+) T lymphocytes was low (ranging from 5 to 12%), about half of pulmonary gamma delta T cells coexpressed it. These cells produced IL-4 and negligible amounts of interferon-gamma (IFN gamma), and proliferated in vitro in response to purified specific but not unrelated allergens. In contrast, control or sarcoidosis gamma delta T cells never displayed the CD30 surface molecule or produced significant quantities of IL-4. CONCLUSIONS: These findings not only confirm our previous hypothesis that the allergen-specific Th2-type lymphocytes found in the lungs of asthmatic patients are gamma delta T cells belonging to airway mucosal immunocytes, but also strongly support the notion that asthma is a local rather than a systemic disease.

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Selected References

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  • McFadden ER, Jr, Gilbert IA. Asthma. N Engl J Med. 1992 Dec 31;327(27):1928–1937. [PubMed]
  • Del Prete G. Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy. Allergy. 1992 Oct;47(5):450–455. [PubMed]
  • Romagnani S. Regulation and deregulation of human IgE synthesis. Immunol Today. 1990 Sep;11(9):316–321. [PubMed]
  • Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. [PubMed]
  • Okuda M, Pawankar R. Flow cytometric analysis of intraepithelial lymphocytes in the human nasal mucosa. Allergy. 1992 Jun;47(3):255–259. [PubMed]
  • Spits H, Paliard X, Vandekerckhove Y, van Vlasselaer P, de Vries JE. Functional and phenotypic differences between CD4+ and CD4- T cell receptor-gamma delta clones from peripheral blood. J Immunol. 1991 Aug 15;147(4):1180–1188. [PubMed]
  • Gascan H, Aversa GG, Gauchat JF, Van Vlasselaer P, Roncarolo MG, Yssel H, Kehry M, Spits H, De Vries JE. Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4. Eur J Immunol. 1992 May;22(5):1133–1141. [PubMed]
  • Wen L, Roberts SJ, Viney JL, Wong FS, Mallick C, Findly RC, Peng Q, Craft JE, Owen MJ, Hayday AC. Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells. Nature. 1994 Jun 23;369(6482):654–658. [PubMed]
  • Horner AA, Jabara H, Ramesh N, Geha RS. gamma/delta T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes. J Exp Med. 1995 Mar 1;181(3):1239–1244. [PMC free article] [PubMed]
  • Montefort S, Gratziou C, Goulding D, Polosa R, Haskard DO, Howarth PH, Holgate ST, Carroll MP. Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways. J Clin Invest. 1994 Apr;93(4):1411–1421. [PMC free article] [PubMed]
  • Spinozzi F, Bertotto A. Cellular mechanisms in the pathogenesis of bronchial asthma. Immunol Today. 1995 Aug;16(8):407–408. [PubMed]
  • 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. [PubMed]
  • Spinozzi F, Cimignoli E, Gerli R, Agea E, Bertotto A, Rondoni F, Grignani F. IgG subclass deficiency and sinopulmonary bacterial infections in patients with alcoholic liver disease. Arch Intern Med. 1992 Jan;152(1):99–104. [PubMed]
  • Bertotto A, Gerli R, Spinozzi F, Muscat C, Scalise F, Castellucci G, Sposito M, Candio F, Vaccaro R. Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection. Eur J Immunol. 1993 May;23(5):1177–1180. [PubMed]
  • Spinozzi F, Agea E, Bassotti G, Belia S, Rondoni F, Broccucci L, Solinas A, Gerli R, Bertotto A. Ethanol-specific impairment of T-lymphocyte activation is caused by a transitory block in signal-transduction pathways. Gastroenterology. 1993 Nov;105(5):1490–1501. [PubMed]
  • Qian D, Sperling AI, Lancki DW, Tatsumi Y, Barrett TA, Bluestone JA, Fitch FW. The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11875–11879. [PubMed]
  • Moffatt MF, Hill MR, Cornélis F, Schou C, Faux JA, Young RP, James AL, Ryan G, le Souef P, Musk AW, et al. Genetic linkage of T-cell receptor alpha/delta complex to specific IgE responses. Lancet. 1994 Jun 25;343(8913):1597–1600. [PubMed]
  • Sandford AJ, Shirakawa T, Moffatt MF, Daniels SE, Ra C, Faux JA, Young RP, Nakamura Y, Lathrop GM, Cookson WO, et al. Localisation of atopy and beta subunit of high-affinity IgE receptor (Fc epsilon RI) on chromosome 11q. Lancet. 1993 Feb 6;341(8841):332–334. [PubMed]
  • Schild H, Mavaddat N, Litzenberger C, Ehrich EW, Davis MM, Bluestone JA, Matis L, Draper RK, Chien YH. The nature of major histocompatibility complex recognition by gamma delta T cells. Cell. 1994 Jan 14;76(1):29–37. [PubMed]
  • Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, Fournié JJ. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994 Apr 8;264(5156):267–270. [PubMed]
  • Del Prete G, De Carli M, Almerigogna F, Daniel CK, D'Elios MM, 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]
  • Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature. 1995 Jan 19;373(6511):255–257. [PubMed]

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