The Role of Regulatory T Cells in Respiratory Infections and Allergy and Asthma
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The role of distinct CD4+ T-cell populations in regulating the nature and strength of immune responses is well documented and in the past has principally focused on the cross-regulation of T-helper type 1 (Th1) and Th2 cells, which secrete interferon-γ and interleukin-4, respectively. However, the identification of T cells capable of suppressing responses mediated by Th1 and Th2 cells, termed regulatory T cells (Treg cells), has prompted a paradigm shift in our understanding of the regulation of immune responses to infection and environmental antigens. This article focuses on the role of Treg cells in the lungs following infection with respiratory pathogens and discusses the targeting of Treg cells in the development of new therapies for immune-mediated respiratory diseases, such as allergy and asthma.
KeywordsRegulatory T cell Tolerance IL-10 TGF-β Immune modulation Infection Bacteria Parasite Allergy Asthma
Dr. McGuirk is an employee of Opsona Therapeutics.
Dr. Mills is a cofounder, a minority shareholder in, a consultant for, and a member of the scientific advisory board for Opsona Therapeutics.
This work was supported by Science Foundation Ireland.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 22.Barrat FJ, Cua DJ, Boonstra A, et al.: In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Exp Med 2002, 195:603–616.CrossRefPubMedGoogle Scholar
- 31.•• Veldhoen M, Uyttenhove C, van Snick J, et al.: Transforming growth factor-beta “reprograms” the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008, 9:1341–1346. The identification of a novel population of CD4 + T cells that secrete IL-9, termed Th9 cells, may prove to be very important in the pathogenesis of allergic disorders.CrossRefPubMedGoogle Scholar
- 34.Fukaura H, Kent SC, Pietrusewicz MJ, et al.: Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J Clin Invest 1996, 98:70–77.CrossRefPubMedGoogle Scholar
- 43.McGuirk P, McCann C, Mills KH: Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 2002, 195:221–231.CrossRefPubMedGoogle Scholar
- 53.Qin XJ, Shi HZ, Liang QL, et al.: CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion. Chin Med J (Engl) 2008, 121:581–586.Google Scholar
- 57.McGuirk P, Mahon BP, Griffin F, Mills KH: Compartmentalization of T cell responses following respiratory infection with Bordetella pertussis: hyporesponsiveness of lung T cells is associated with modulated expression of the co-stimulatory molecule CD28. Eur J Immunol 1998, 28:153–163.CrossRefPubMedGoogle Scholar
- 70.• Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT: Grass pollen immunotherapy induces FoxP3-expressing CD4+ CD25+ cells in the nasal mucosa. J Allergy Clin Immunol 2008, 121:1467–1472. This article demonstrates the potential of immunotherapeutic approaches for allergies based on Treg induction.CrossRefPubMedGoogle Scholar
- 73.•• Wakashin H, Hirose K, Maezawa Y, et al.: IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med 2008, 178:1023–1032. This article reports that Th17 cells may cooperate with Th2 cells to induce neutrophilic and eosinophilic airway inflammation.CrossRefPubMedGoogle Scholar