The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells

Li Zhou,Qing-Sheng Mi,Ashok Sharma,Xing Zhong,Nikhil Garge,Jin-Xiong She,Hongjie Wang,Richard A Mcindoe,Robert Podolsky,Yulan Jin

doi:10.1186/gb-2008-9-7-r119

Abstract

Global gene expression profiling of in vitro cultured CD8+ T cells that express natural killer cell markers revealed differential expression of about 3,000 genes between these cells and naïve CD8+ T cells.

Highlights

CD8+ natural killer T cell (NKT)-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers
We can efficiently produce, from the total splenic CD8+ T cell population, large numbers of CD8+ T cells that coexpress various NK markers. These cells are referred to as CD8+ NKT-like cells. We demonstrate that these cells possess potent immunosuppressive activity and report the molecular profiles of these cells assayed using microarray analysis coupled with multiple confirmation techniques, including RT-PCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry
In vitro culture of CD8+ T cells In vitro cultures with anti-CD3/anti-CD28-coated beads in the presence of high dose IL-2 can efficiently expand CD4+CD25+ regulatory T (Treg) cells that suppress the proliferation of effector T cells

Summary

Introduction

CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. The first population is the well-characterized invariant NKT (iNKT) cells that express invariant Vα14-Jα18 TCR in mice [8,9,10] These iNKT cells are restricted by the major histocompatibility complex (MHC) class I-like molecule Cd1d and recognize glycolipid antigen α-galactosylceramide, a synthetic variant of a murine sponge-derived glycolipid [8,11]. These iNKT cells produce large amounts of interleukin (IL)-4 and interferon (IFN)-γ upon activation and have been shown to play a critical role in regulating the immune response [8,11]. It has been shown that neonatal tolerance is associated with increased CD8+ NKT-like cells, suggesting that CD8+ NKT-like cells may have immunoregulatory properties [12]

Methods

Results

Discussion

Conclusion