Paralysis of CD4(+)CD25(+) regulatory T cell response in chronic autoimmune encephalomyelitis.
Increasing evidence strongly suggest that CD4(+)CD25(+) regulatory T (Treg) cells play a pivotal role in suppressing the development of autoimmune diseases. However, it remains poorly understood how these cells are involved in the persistence of, or recovery from, the diseases. In the present study, we examined the role of CD4(+)CD25(+) Treg cells in chronic EAE and compared the results with those obtained in acute EAE. In EAE lesions, CD25(+) cells decreased rapidly at the beginning of chronic EAE, whereas these cells were maintained at high levels during the recovery from acute EAE. The number of Foxp3(+)CD4(+)CD25(+) Treg and levels of Foxp3 mRNA in the lymphoid organ were significantly lower in chronic EAE. Importantly, the regulatory function of individual CD4(+)CD25(+) Treg cells was maintained in animals with chronic EAE. Furthermore, adoptive transfer of activated CD4(+)CD25(+) Treg cells suppressed the development of chronic EAE. These findings suggest that impairment of the CD4(+)CD25(+) Treg response is critical for development of chronic autoimmune diseases, and can be adjustable by autologous Treg transplantation.
Matsumoto
Yoh
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan. matyoh@tmin.ac.jp
Sakuma
Hiroshi
H
Kohyama
Kuniko
K
Park
Il-Kwon
IK
D019264:Adoptive Transfer; D000818:Animals; D030801:Animals, Genetically Modified; D015704:CD4 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008198:Lymph Nodes / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000235:genetics; D010243:Paralysis / Q000209:etiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D053645:Interleukin-2 Receptor alpha Subunit