In Vitro Induction of Regulatory CD4+CD8α+ T Cells by TGF-β, IL-7 and IFN-γ

Abstract

In vitro CD4+ T cell differentiation systems have made important contributions to understanding the mechanisms underlying the differentiation of naive CD4+ T cells into effector cells with distinct biological functions. Mature CD4+ T cells expressing CD8αα homodimers are primarily found in the intestinal mucosa of men and mice, and to a lesser extent in other tissues such as peripheral blood. Although CD4+CD8α+ T cells are easily identified, very little is known about their development and immunological functions. It has been reported, however, that CD4+CD8α+ T cells possess regulatory properties. In this report, we present a novel in vitro differentiation system where CD4+ T cells are stimulated to become CD4+CD8α+ T cells in the presence of TGF-β, IL-7 and IFN-γ, resulting in cells with very similar features as CD4+CD8α+ intraepithelial lymphocytes. This novel in vitro differentiation culture should provide a powerful and tractable tool for dissecting the differentiation and biological functions of CD4+CD8α+ T cells.