Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+ CD25+ regulatory cells within the central nervous system

MJ McGeachy, LA Stephens… - The Journal of …, 2005 - journals.aai.org
MJ McGeachy, LA Stephens, SM Anderton
The Journal of Immunology, 2005journals.aai.org
Immune regulation of autoimmune disease can function at two sites: at the secondary
lymphoid organs or in the target organ itself. In this study, we investigated the natural
resolution of autoimmune pathology within the CNS using murine experimental autoimmune
encephalomyelitis (EAE). Recovery correlates with the accumulation of IL-10-producing
CD4+ CD25+ T cells within the CNS. These CD4+ CD25+ cells represent as many as one in
three of CD4+ cells in the CNS during recovery, they are FoxP3+ and express other markers …
Abstract
Immune regulation of autoimmune disease can function at two sites: at the secondary lymphoid organs or in the target organ itself. In this study, we investigated the natural resolution of autoimmune pathology within the CNS using murine experimental autoimmune encephalomyelitis (EAE). Recovery correlates with the accumulation of IL-10-producing CD4+ CD25+ T cells within the CNS. These CD4+ CD25+ cells represent as many as one in three of CD4+ cells in the CNS during recovery, they are FoxP3+ and express other markers associated with regulatory cells (CTLA-4, GITR, and α E β 7), and they have regulatory function ex vivo. Depletion of CD25+ cells inhibits the natural recovery from EAE. Also, depletion of CD25+ cells after recovery removes the resistance to reinduction of EAE observed in this model. Furthermore, passive transfer of CNS-derived CD4+ CD25+ cells in low numbers provides protection from EAE in recipient mice. These are the first data demonstrating the direct involvement of CD4+ CD25+ regulatory T cells in the natural resolution of autoimmune disease within the target organ.
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