Concepedia

In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes

Qizhi Tang, Kammi Henriksen, Mingying Bi, Erik B. Finger, Jianqin Ye, Emma L. Masteller, Hugh O. McDevitt, Mark Bonyhadi, Jeffrey A. Bluestone

The Journal of Experimental Medicine · 2004 · 1.2K citations · 49 references

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TL;DR

The low number, anergic phenotype, and diverse antigen specificity of CD4⁺CD25⁺ regulatory T cells hinder their therapeutic use in autoimmunity and transplant rejection. This study develops a robust method to expand antigen‑specific Tregs from autoimmune‑prone non‑obese diabetic mice. Purified CD4⁺CD25⁺ Tregs were expanded up to 200‑fold in less than two weeks in vitro using anti‑CD3, anti‑CD28, and IL‑2. The expanded Tregs display a classical phenotype, suppress effector T cells in vitro and in vivo, and small numbers of antigen‑specific Tregs can reverse diabetes after onset, indicating a novel cellular immunotherapy for autoimmunity.

Abstract

The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ Tregs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded Tregs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.