The effector T helper cell triade.
T lymphocytes play crucial role in immune responses. Effector T helper (Th) cells derive from progenitor naïve CD4+ T cells, after maturational process induced by antigenic stimulation. Their commitment depends on complex interactions with antigen-presenting cells in a permissive milieu, including antigenic type and load, costimulatory molecules and cytokine signaling. Committed CD4+ T cells may differentiate into Th1, Th2, TH17 phenotypes (the effector Th cell triade), with distinct cytokine products and biological functions, or evolve into the inducible regulatory T (Treg) lineage, with immunomodulatory functions. Th1 subset, primarily addressed to face intracellular pathogens, produces interleukin (IL)-2, IL-3, interferon-gamma and tumour necrosis factor-beta, peculiarly supporting cellular immunity. Th2 cells, essential in eliminating extracellular pathogens, including helminthes, express IL-4, IL-5, IL-6, IL-10, IL-13, and IL-25, supporting humoral immunity. Th17 subset, determinant in fighting Gram-negative bacteria, fungi, and some protozoa, secretes IL-17, IL-21, and IL-22, with strong proinflammatory effects. Th responses are tightly controlled to avoid self antigen reactivity or excessive reactions to non-self antigens. In fact, dysregulated Th1 response drives cell-mediated autoimmune disorders, and enhanced Th2 activity is involved in atopy, whereas Th17 cells are probably responsible for chronic tissue inflammation. Skewing of response away from Treg cells may lead to the onset and/or progression of autoimmune diseases or acute transplant rejection in humans. A better understanding of Th triade functions, and a clearer definition of Th response regulatory mechanisms may provide novel therapeutic opportunities in treating immunopathologies.
Fietta
Pieranna
P
Dipartimento Medico Polispecialistico 2, S.D. di Medicina Interna e Reumatologia, Azienda Ospedaliera Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy. farnese15@libero.it
Delsante
Giovanni
G
D001327:Autoimmune Diseases / Q000276:immunology*; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006410:Hematopoiesis; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008954:Models, Biological; D018448:Models, Immunological; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines