B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

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 (TFH cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of TFH cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F1 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 TFH 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 TFH cell pool is an important mechanism by which ICOS regulates Ab production.