B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis

The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T-cell programmed death (PD)-1 recognition of B7-H1 (PD-L1) expressed on APC and non-lymphoid tissue regulates T-cell activation. We show that B7-H1 ^-/- mice exhibit exacerbated proteoglycan (PG)-induced arthritis and increased Th-1 CD4 ⁺ T-cell responses. Unexpectedly, the PG-specific antibody response in B7-H1 ^-/-1 mice was diminished. A reduction in the number of peanut agglutinin ¹ GC coincided with a decrease in CD19 ⁺ GL-7 ⁺ CD95 ⁺ GC B cells that was a result of increased caspase-induced apoptosis. The percent of CD38 ⁺ CD138 ⁺ emerging plasma cells was decreased. B7-H1 ^-/- mice exhibited an increased frequency of CD4 ⁺ PD-1 ^hi CXCR5 ^hi ICOS ^hi CD62L ^lo T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL-21, and the apoptosis-inducer molecule FasL. In cell transfer of B7-H1 ^-/- cells into SCID mice, non-B and non-T cells were sufficient to normalize the antibody response, T-cell hyperactivity, and the development of PG-induced arthritis. These findings indicate that B7-H1 on non-B and non-T cells signals through PD-1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7-H1 expression in promoting B-cell survival by regulating the activation of T follicular helper cell.