Identification of T helper type 1-like, [Foxp3.sup.+] regulatory T cells in human autoimmune disease

[CD4.sup.+] [CD25.sup.high] [CD127.sup.low/-] forkhead box p3 [(Foxp3).sup.+] regulatory T cells ([T.sub.reg] cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 ([T.sub.H]1)-like, interferon-γ (IFN-γ)-secreting [Foxp3.sup.+] 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.sup.+] [Foxp3.sup.+] T cells is similar to that in healthy control subjects. In vitro, human [T.sub.reg] cells from healthy subjects acquire a [T.sub.H]1-like phenotype when cultured in the presence of interleukin-12 (IL-12). [T.sub.H]1-like [T.sub.reg] cells show reduced suppressive activity in vitro, which can partially be reversed by IFN-γ-specific antibodies or by removal of IL-12.
Multiple sclerosis is a genetically mediated chronic inflammatory disease of the central nervous system (CNS). Activated [CD4.sup.+] inflammatory cells in the circulation of affected individuals infiltrate into the CNS and [...]