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

Eur J Immunol. 2010 Nov;40(11):3117-27. doi: 10.1002/eji.201040690. Epub 2010 Oct 27.

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(-/-) mice was diminished. A reduction in the number of peanut agglutinin(+) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / metabolism
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology*
  • B7-1 Antigen / metabolism
  • B7-H1 Antigen
  • Cell Survival / genetics
  • Cell Survival / immunology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, SCID
  • Peptides / genetics
  • Peptides / immunology*
  • Peptides / metabolism
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / pathology

Substances

  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-H1 Antigen
  • Bcl6 protein, mouse
  • Cd274 protein, mouse
  • DNA-Binding Proteins
  • Interleukins
  • Membrane Glycoproteins
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • interleukin-21