Abstract

Treatment with ex vivo–generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)_35–55/IA^b (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer–reactive, Foxp3⁺ T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3⁺ T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4⁺Foxp3⁺ T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.

1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
2. Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
3. Malaghan Institute of Medical Research, P.O. Box 7060, Wellington South, New Zealand.
4. Laboratory Service, Veterans Affairs Health Care System, Palo Alto, California 94304, and Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
5. Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
6. These authors contributed equally to this work.

Correspondence to: Mohamed Oukka^1,6 e-mail: moukka@rics.bwh.harvard.edu

Correspondence to: Vijay K Kuchroo^1,6 e-mail: vkuchroo@rics.bwh.harvard.edu

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