The role of T lymphocytes in the pathogenesis of asthma.
There is considerable evidence to support a role for T cells in asthma, particularly the involvement of T(H)2 cells both in atopic allergic asthma and in nonatopic and occupational asthma. There might also be a minor contribution from T(C)2 CD8+ T cells. Several T(H)2 cytokines have the potential to modulate airway inflammation, particularly IL-13, which induces airway hyperresponsiveness independently of IgE and eosinophilia in animal models. The identification of transcription factors controlling T(H)1 and T(H)2 development further support the T(H)2 hypothesis because GATA3 is overexpressed and T-bet is underexpressed in the asthmatic airway. Specific T cell directed immunotherapy might allow induction, modulation, or both of T-cell responses, and elucidation of the mechanisms of regulatory T cells might allow further optimization of immunotherapy. Recent advances in our understanding of dendritic cell function in directing T-cell responses might uncover further therapeutic targets. The efficacy of cyclosporin A and anti-CD4 treatment in patients with chronic severe asthma argues for continued T-cell involvement, but whether remodeling contributes to pathology inaccessible to anti-inflammatory treatment or T-cell immunotherapy will be an important future question.
Larché
Mark
M
Department of Allergy and Clinical Immunology, Faculty of Medicine, Imperial College London, National Heart and Lung Institute, London, United Kingdom.
Robinson
Douglas S
DS
Kay
A Barry
AB
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D010641:Phenotype; D013601:T-Lymphocytes / Q000502:physiology*; D018418:Th2 Cells / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine