T cell directives for transcriptional regulation in asthma.
Allergic asthma frequently starts in childhood, and environmental factors such as viruses, allergens and occupational exposure can regulate the evolution of the disease. The development of allergen-specific Th2 lymphocytes represents the triggering event for the recruitment and activation of IgE-producing B cells and fibroblasts, followed by the release of soluble factors, thus giving rise to the inflammatory reaction observed in this disease. GATA-3 was identified as a cell lineage-specific factor selectively expressed and activated in the Th2 lineage as a consequence of STAT-6 activation. However, recent literature indicates that blockade of CTLA-4-directed inhibitory signals is sufficient to induce STAT 6-independent Th2 differentiation. A new Th1-restricted transcription factor has been recently identified that transactivates the IFN-gamma gene promoter: T-bet (T-box expressed in T cells). T-bet expression during T cell activation is strongly dependent on IFN-gamma and STAT-1. Mice lacking T-bet have profound defects in the development of the Th1 subset and the production of IFN-gamma, but overproduce Th2 cytokines and, in the absence of immunological challenge, they exhibited airway hyperreactivity to methacholine associated with a peribronchial and perivascular infiltration with eosinophils and lymphocytes. Finally, a small subset of CD4 T cells called T-regulatory (T-reg) cells has been identified. These cells exhibit potent immunosuppressive properties. Although recent reports suggest that the induction of T-reg cells is under the control of the transcription factor Foxp3, the specific signals that preferentially induce development of T-reg cells instead of Th2 cells are still unclear.
Finotto
Susetta
S
I Medical Clinic, Laboratory of Immunology, Verfügungsgebäude für Forschung und Entwicklung, University of Mainz, Germany. finotto@mail.uni-mainz.de
Glimcher
Laurie
L
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology*