B7RP-1 blockade ameliorates autoimmunity through regulation of follicular helper T cells.
J Immunol
; 182(3): 1421-8, 2009 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-19155489
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Transdução de Sinais
/
Diferenciação Celular
/
Linfócitos T Auxiliares-Indutores
/
Antígeno B7-1
/
Centro Germinativo
/
Anticorpos Bloqueadores
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos