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

Keith M. Hamel, Yanxia Cao, Yumei Wang, Rachel Rodeghero, Tamas Kobezda, Lieping Chen, Alison Finnegan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3117-3127
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number11
DOIs
StatePublished - 2010

Keywords

  • Antibodies
  • B cells
  • B7-H1
  • Inflammation
  • T follicular helper cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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