Document Detail


B7RP-1 blockade ameliorates autoimmunity through regulation of follicular helper T cells.
MedLine Citation:
PMID:  19155489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autoimmune diseases are marked by the presence of class-switched, high-affinity autoantibodies with pathogenic potential. Costimulation plays an important role in the activation of T cells and the development of T cell-dependent B cell responses. ICOS plays an indispensable role in the development of follicular helper T cells (T(FH) cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of T(FH) cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F(1) mouse model of systemic lupus erythematosus and the collagen-induced arthritis model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP-1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations and leads to a decrease in T(FH) cells and GC B cells as well as an overall decrease in the frequency of ICOS(+) T cells. Coculture experiments of Ag-primed B cells with CXCR5(+) or CXCR5(-) T cells show that blocking B7RP-1 does not directly impact the production of IgG by B cells. These findings further support the role of ICOS in autoimmunity and suggest that the expansion of the T(FH) cell pool is an important mechanism by which ICOS regulates Ab production.
Authors:
Yi-Ling Hu; Daniela P Metz; James Chung; Gerald Siu; Ming Zhang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  182     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-21     Completed Date:  2009-03-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1421-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Inflammation, Amgen, Inc., Thousand Oaks, CA 91320, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Blocking / administration & dosage*
Antibodies, Monoclonal / administration & dosage*
Antigens, CD80 / immunology*,  physiology
Antigens, Differentiation, T-Lymphocyte / immunology,  physiology
Arthritis, Experimental / immunology,  pathology,  therapy
Autoantibodies / biosynthesis*,  metabolism
B-Lymphocytes / immunology,  metabolism,  pathology
Cell Differentiation / immunology*
Female
Germinal Center / immunology*,  metabolism,  pathology
Lupus Erythematosus, Systemic / immunology,  pathology,  therapy
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Mice, Inbred NZB
Random Allocation
Signal Transduction / immunology*
T-Lymphocytes, Helper-Inducer / immunology*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Antibodies, Blocking; 0/Antibodies, Monoclonal; 0/Antigens, CD80; 0/Antigens, Differentiation, T-Lymphocyte; 0/Autoantibodies; 0/B7-related protein-1; 0/inducible T-cell co-stimulator

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


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