Fc Receptor-Like 3 Protein Expressed on IL-2 Nonresponsive Subset of Human Regulatory T Cells

Abstract

Fc receptor-like 3 (FCRL3) is a cell surface protein homologous to Fc receptors. The FCRL3 gene is present in humans but not in mice. We found that FCRL3 protein is expressed on 40% of human naturally occurring CD4+ regulatory T (nTreg) cells (CD4+CD25+CD127low). Sorted nTreg cells with the surface phenotype FCRL3+ and FCRL3− were both hypoproliferative to TCR stimulation and both suppressive on proliferation of conventional T cells (CD4+CD25−) in vitro. They both expressed forkhead box p3 (Foxp3) protein, the intracellular regulatory T cell marker. However, in contrast to FCRL3− nTreg cells, FCRL3+ nTreg cells were not stimulated to proliferate by the addition of exogenous IL-2. In addition, Foxp3+ cells induced from conventional T cells by TGF-β treatment did not exhibit FCRL3 expression. These results suggest that the FCRL3+ subset of human nTreg cells identified in this study arise in vivo and Foxp3 expression alone is not sufficient to induce FCRL3 expression. FCRL3 may be involved in human-specific mechanisms to control the generation of nTreg cells.