B cell-specific expression of inducible costimulator ligand is necessary for the induction of arthritis in mice.
OBJECTIVE
Inducible costimulator (ICOS)-ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced arthritis (PGIA).


METHODS
PGIA was initiated by immunizing wild-type and ICOSL-deficient (ICOSL(-/-) ) or B cell-specific ICOSL(-/-) chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies.


RESULTS
Arthritis progression was completely inhibited in both ICOSL(-/-) mice and B cell-specific ICOSL(-/-) chimeric mice. Production of the Teff cell-produced cytokines interferon-γ and interleukin-17 (IL-17) and the antiinflammatory cytokine IL-4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL-21 correlated with a decrease in the anti-mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses.


CONCLUSIONS
These data indicate that the signals provided by ICOSL-expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL-ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.
University of Chicago, Chicago, Illinois.
Keith M
KM
Hamel
Yanxia
Y
Cao
Susan A
SA
Olalekan
Alison
A
Finnegan
D000276:Adjuvants, Immunologic; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011509:Proteoglycans; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D011509:Proteoglycans