| First Author | Hu YL | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 3 | Pages | 1421-8 |
| PubMed ID | 19155489 | Mgi Jnum | J:144328 |
| Mgi Id | MGI:3830752 | Doi | 10.4049/jimmunol.182.3.1421 |
| Citation | Hu YL, et al. (2009) B7RP-1 blockade ameliorates autoimmunity through regulation of follicular helper T cells. J Immunol 182(3):1421-8 |
| abstractText | 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. |
