Different CD4+ Treg subsets, different suppressive abilities: A comparison of CD27+CD127- and CD39+ Treg cells (65.3)

Abstract

Abstract T regulatory (Treg) cells are important in the development of autoimmunity. They are usually identified by their expression of CD25 and Foxp3, although functionally and phenotypically diverse subsets exist. To identify human Treg subsets we analyzed expression of CD27, CD127, CD39, and CTLA4 on CD4 T cells. A CD27+CD127- phenotype correlates with high CD25 and Foxp3 expression. CD39 expression is higher on CD25hi than on CD25med/lo T cells. We co-cultured sorted Treg subsets with T effector (Teff) cells to study suppression of proliferation and cytokine production. CD4+CD25hiCD27+CD127- Treg cells were suppressive of both Teff cell proliferation and cytokine production when activated with anti-CD3 and anti-CD28. CD39+ Treg cells did not inhibit Teff cell proliferation under these culture conditions, but did suppress proliferation and cytokine production when activated with anti-CD3 and antigen-presenting cells (APCs). The varied suppressive abilities of Treg cells in these different culture conditions may be a result of the ability of APCs, but not anti-CD28, to signal through the negative costimulatory molecule CTLA4. We are currently investigating the function of CTLA4 in these Treg populations. We also examined whether these Treg subsets vary in their cytokine profile. Elucidating Treg mechanisms and subsets will enable us to clarify how Treg cells suppress, how they are altered in autoimmunity, and ultimately how this defect can be overcome to treat autoimmunity.