Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease

• Published in: Nature medicine Vol. 17; no. 6; pp. 673 - 675
• Main Authors: Dominguez-Villar, Margarita, Baecher-Allan, Clare M, Hafler, David A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2011; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1271; 631/250/38; 692/699/249/1313/1666; Autoantibodies - immunology; Autoimmune diseases; Biomedical and Life Sciences; Biomedical research; Biomedicine; brief-communication; Cancer Research; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - physiology; Humans; Immunity, Cellular - immunology; Infectious Diseases; Interferon; Interferon-beta - therapeutic use; Interferon-gamma - immunology; Interleukin-12 - physiology; Metabolic Diseases; Molecular Medicine; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurosciences; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - physiology; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - physiology
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.2389

In mice, T regulatory (T reg ) cells show considerable phenotypic and functional plasticity. David Hafler and his colleagues report that the frequency of human T reg cells expressing IFN-γ is increased in the peripheral blood of individuals with multiple sclerosis. These T reg cells possess reduced suppressive activity, and in vitro studies suggest that IL-12 promotes the development of a T helper type 1–like phenotype. CD4 + CD25 high CD127 low/– forkhead box p3 (Foxp3) + regulatory T cells (T reg cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 (T H 1)-like, interferon-γ (IFN-γ)-secreting Foxp3 + T cells in untreated subjects with relapsing remitting multiple sclerosis (RRMS) as compared to healthy control individuals. In subjects treated with IFN-β, the frequency of IFN-γ + Foxp3 + T cells is similar to that in healthy control subjects. In vitro , human T reg cells from healthy subjects acquire a T H 1-like phenotype when cultured in the presence of interleukin-12 (IL-12). T H 1-like T reg cells show reduced suppressive activity in vitro , which can partially be reversed by IFN-γ–specific antibodies or by removal of IL-12.