T regulatory cells (Tregs) are important in the development and progression of autoimmunity. Tregs are usually identified by their expression of CD25 and Foxp3, although functionally and phenotypically diverse subsets exist. By identifying various subsets we hope to clarify their function and role in autoimmunity. We are also studying the novel cytokine IL-35, which is believed to be integral for Treg function. To identify Treg subsets we analyzed expression of CD27, CD127, and CD39 on CD4 T cells with varying CD25 levels. A CD27+CD127- phenotype correlates highly with CD25 and Foxp3 expression. CD39 expression is higher on CD4+CD25hi T cells than on CD25med/lo cells. We cultured sorted Treg subsets with T effector (Teff) cells to measure suppression. High expression of CD25 was a better marker for suppressive ability than the CD27+CD127- phenotype. CD39+ Tregs did not suppress proliferation when activated with anti-CD3 and anti-CD28, but they did inhibit IFN-γ production. Expression of the IL-35 subunits, EBI3 and p35, was observed in activated Tregs but not resting or activated induced Tregs or Teffs. Studies are ongoing to examine IL-35 in Treg subsets. Elucidating Treg mechanisms and subsets will enable us to clarify how Tregs suppress, how they are defective in autoimmunity, and ultimately how this defect can be overcome to treat autoimmunity.
- Copyright © 2011 by The American Association of Immunologists, Inc.