Document Detail


Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells.
MedLine Citation:
PMID:  23376792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current therapies to treat autoimmune disease focus mainly on downstream targets of autoimmune responses, including effector cells and cytokines. A potentially more effective approach would entail targeting autoreactive T cells that initiate the disease cascade and break self tolerance. The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60(p216) and Qdm. We found that peptide-induced expansion of tetramer-binding CD8(+) Tregs that recognize Qa-1-Hsp60(p216) but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (T(FH)) and Th17 cells by CD8(+) Tregs inhibited disease development. Infusion of in vitro-expanded CD8(+) Tregs increased the efficacy of methotrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-1-Hsp60(p216)-specific CD8(+) Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60(p216) peptide immunization. These results suggest that strategies designed to expand Qa-1-restricted (HLA-E-restricted), peptide-specific CD8(+) Tregs represent a promising therapeutic approach to autoimmune disorders.
Authors:
Jianmei W Leavenworth; Xiaolei Tang; Hye-Jung Kim; Xiaoyang Wang; Harvey Cantor
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-08
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-05-13     Revised Date:  2013-10-24    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1382-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Experimental / immunology,  prevention & control*
CD8-Positive T-Lymphocytes / immunology*,  physiology,  transplantation
Cells, Cultured
Chaperonin 60 / genetics,  immunology
Histocompatibility Antigens Class I / immunology
Humans
Immunization
Interleukin-15 / metabolism
Male
Methotrexate / pharmacology
Mice
Mice, Inbred C57BL
Mitochondrial Proteins / genetics,  immunology
Mutation, Missense
Peptide Fragments / immunology*
Peptides / immunology
Perforin / metabolism
T-Lymphocytes, Regulatory / immunology*,  physiology,  transplantation
Th17 Cells / immunology
Grant Support
ID/Acronym/Agency:
AI 037562/AI/NIAID NIH HHS; R01 AI037562/AI/NIAID NIH HHS; T32 CA 009382/CA/NCI NIH HHS; T32 CA070083/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Chaperonin 60; 0/Histocompatibility Antigens Class I; 0/Hspd1 protein, mouse; 0/Interleukin-15; 0/Mitochondrial Proteins; 0/Peptide Fragments; 0/Peptides; 0/Q surface antigens; 0/Qdm protein, mouse; 126465-35-8/Perforin; 59-05-2/Methotrexate
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  CXCL5 limits macrophage foam cell formation in atherosclerosis.
Next Document:  Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling.