TitleAlterations in regulatory T-cells: rediscovered pathways in immunotoxicology.
Publication TypeJournal Article
Year of Publication2011
AuthorsCorsini E, Oukka M, Pieters R, Kerkvliet NI, Ponce R, Germolec DR
JournalJ Immunotoxicol
Date Published2011 Oct-Dec
KeywordsAnimals, Antigen Presentation, Autoantigens, Autoimmune Diseases, Biomarkers, Dendritic Cells, Environmental Pollutants, Guinea Pigs, Hypersensitivity, Immunity, Cellular, Immunosuppression, Mice, Polychlorinated Dibenzodioxins, Rats, T-Lymphocytes, Regulatory

In addition to the effector T-cells subsets, T-cells can also differentiate into cells that play a suppressive or regulatory role in adaptive immune responses. The cell types currently identified as regulatory T-cells (T(regs)) include natural or thymic-derived T(regs), T-cells which express Foxp3(+)CD25(+)CD4(+) and can suppress immune responses to autoreactive T-cells, as well as inducible T(regs), that are generated from naïve T-cells in the periphery after interaction with antigens presented by dendritic cells. Inducible T(regs) include T(H)3 cells, T(r)1 cells, and Foxp3(+)-inducible T(regs). T(regs) have been shown to be critical in the maintenance of immune responses and T-cell homeostasis. These cells play an important role in suppressing responses to self-antigens and in controlling inappropriate responses to non-self-antigens, such as commensal bacteria or food in the gut. For example, depletion of CD4(+)CD25(+) T(regs) from mice resulted in the development of multi-organ autoimmune diseases. CD4(+)CD25(+) T(regs) and/or IL-10-producing T(r)1 cells are capable of suppressing or attenuating T(H)2 responses to allergens. Moreover, adoptive transfer of CD4(+)CD25(+) T(regs) from healthy to diseased animals resulted in the prevention or cure of certain autoimmune diseases, and was able to induce transplantation tolerance. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma is associated with the induction of IL-10- and TGFβ-producing T(r)1 cells as well as FoxP3-expressing IL-10 T-cells, with resulting suppression of the T(H)2 cytokine milieu. Activation, expansion, or suppression of CD4(+)CD25(+) T(regs) in vivo by xenobiotics, including drugs, may therefore represent a relevant mechanism underlying immunotoxicity, including immunosuppression, allergic asthma, and autoimmune diseases.

Alternate JournalJ Immunotoxicol
PubMed ID21848365
PubMed Central IDPMC3448276
Grant ListZ99 ES999999 / / Intramural NIH HHS / United States