Recovery from experimental allergic encephalomyelitis is TGF-beta dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells.
SJL mice are highly susceptible to proteolipid protein (PLP) 139-151-induced experimental allergic encephalomyelitis (EAE). The disease is characterized by a relapsing-remitting type of paralysis. However, the mechanism by which animals recover from EAE is poorly understood. Here, we investigated the role of regulatory T cells in the recovery from disease. We found that Forkhead box P3-expressing CD4+CD25+ T cells were increased in the blood, draining lymph node and spleen of EAE-recovered SJL mice. These cells were anergic and inhibited proliferation of CD4+CD25- T cells to PLP 139-151 or anti-CD3 antibody stimulation. Depletion of CD4+CD25+ T cells during the recovery phase exacerbated disease, resulted in the expansion of IA(s)/PLP 139-151-tetramer-positive cells and enhanced IFN-gamma production. In addition, transforming growth factor-beta (TGF-beta) was shown to be involved in the recovery from EAE as the percentage of CD4+ cells expressing TGF-beta latency-associated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAE-recovered mice as compared with the naive mice and in vivo neutralization of TGF-beta abolished recovery from disease. Taken together, our results demonstrate that both CD4+CD25+ and CD4+LAP+ regulatory T cells mediate recovery from PLP 139-151-induced EAE in SJL mice in which TGF-beta plays an important role.
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Xingmin
X
Zhang
Jayagopala
J
Reddy
Hirofumi
H
Ochi
Dan
D
Frenkel
Vijay K
VK
Kuchroo
Howard L
HL
Weiner
D019264:Adoptive Transfer; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D020127:Recovery of Function / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta