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Th1/Th17 polarization and acquisition of an arthritogenic phenotype in arthritis-susceptible BALB/c, but not in MHC-matched, arthritis-resistant DBA/2 mice

By Ferenc Boldizsar, Oktavia Tarjanyi, Peter Nemeth, Katalin Mikecz and Tibor T. Glant


Proteoglycan (PG) aggrecan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA). Although BALB/c and DBA/2 mice share the same MHC (H-2d) haplotype, the BALB/c strain is susceptible to PGIA, while DBA/2 mice are resistant. Therefore, these two inbred mouse strains provide an opportunity to study arthritis susceptibility factors excluding the effects of MHC-associated genetic components. The goal of this study was to monitor changes in the cellular composition and activation state following intra-peritoneal (i.p.) immunization to induce PGIA; additionally, we sought to identify new susceptibility factors by comparing PG-induced immune responses in BALB/c and DBA/2 mice. Upon i.p. PG injection, resident naive B1 cells are replaced by both T cells and conventional B cells in the peritoneum of BALB/c mice. These peritoneal T cells produce IFNγ and IL-17, cytokines shown to be important in RA and corresponding arthritis models. Moreover, peritoneal cells can adoptively transfer PGIA to SCID mice, demonstrating their arthritogenic properties. Our results indicate that repeatedly injected antigen leads to the recruitment and activation of immune cells in the peritoneum; these cells then trigger the effector phase of the disease. The migration and activation of Th1/Th17 cells in the peritoneal cavity in response to PG immunization, which did not occur in the arthritis-resistant DBA/2 strain, may be critical factors of arthritis susceptibility in BALB/c mice

Topics: Original Research Papers
Publisher: Oxford University Press
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Provided by: PubMed Central

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  1. (2000). a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.
  2. (2004). Achievement of a synergistic adjuvant effect on arthritis induction by activation of innate immunity and forcing the immune response toward the Th1 phenotype. Arthritis Rheum.
  3. (1991). Adjuvant effects of dimethyl dioctadecyl ammonium bromide, complete Freund’s adjuvant and aluminium hydroxide on neutralizing antibody, antibody-isotype and delayed-type hypersensitivity responses to Semliki Forest virus in mice.
  4. (2006). All in the family: IL-27 suppression of T(H)-17 cells.
  5. (2003). Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice.
  6. (2008). Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells.
  7. (1986). Antigen presentation by B cells and its significance in T-B interactions.
  8. (2005). Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis.
  9. (2006). Antigeninduced differential gene expression in lymphocytes and gene expression profile in synovium prior to the onset of arthritis.
  10. B cell recovery in arthritis adoptively transferred to SCID mice: antigen-specific activation is required for restoration of autopathogenic CD4+ Th1 cells in a syngeneic system.
  11. (2006). B lymphocytes on the front line of autoimmunity.
  12. (1994). CD43 (S7) expression identifies peripheral B cell subsets.
  13. (1995). Cellular composition of milky spots in the human greater omentum: an immunochemical and ultrastructural study.
  14. (2002). Characterization of B-1b cells as antigen presenting cells in the immune response to gp43 from Paracoccidioides brasiliensis in vitro.
  15. (1998). Critical role of glycosaminoglycan side chains of cartilage proteoglycan (aggrecan) in antigen recognition and presentation.
  16. (2008). Cytokinecontrolled RANKL and osteoprotegerin expression by human and Peritoneal factors control susceptibility to PGIA 521mouse synovial fibroblasts: fibroblast-mediated pathologic bone resorption. Arthritis Rheum.
  17. (2002). DDA adjuvant induces a mixed Th1/Th2 immune response when associated with BBG2Na, a respiratory syncytial virus potential vaccine.
  18. (2001). Defense mechanisms of the peritoneal cavity.
  19. (2008). Development of proteoglycan-induced arthritis is independent of IL-17.
  20. (1989). Different T helper cell subsets elicited in mice utilizing two different adjuvant vehicles: the role of endogenous interleukin 1 in proliferative responses.
  21. (1992). Differential development of progenitor activity for three B-cell lineages.
  22. (2000). Generation, expansion, migration and activation of mouse B1 cells.
  23. (2000). High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism.
  24. (1999). Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis. Arthritis Rheum.
  25. (1998). IL-1 alpha and TNF-alpha are required for IL-12-induced development of Th1 cells producing high levels of IFN-gamma in BALB/c but not C57BL/6 mice.
  26. (2001). IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis.
  27. (1999). IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.
  28. (2006). IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis.
  29. IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist.
  30. (2003). IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism.
  31. (1987). Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum.
  32. (2006). Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice. Arthritis Rheum.
  33. (2003). Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17.
  34. (2007). Interleukin-4 regulates proteoglycan-induced arthritis by specifically suppressing the innate immune response. Arthritis Rheum.
  35. (2001). Modes of action of Freund’s adjuvants in experimental models of autoimmune diseases.
  36. Peritoneal factors control susceptibility
  37. (1999). Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.
  38. (2004). Proteoglycan aggrecan-induced arthritis. A murine autoimmune model of rheumatoid arthritis.
  39. (1987). Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum.
  40. (1990). Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice. Arthritis Rheum.
  41. (2003). Proteoglycaninduced arthritis: immune regulation, cellular mechanisms and genetics.
  42. (1994). Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages.
  43. (2000). Role of natural and immune IgM antibodies in immune responses.
  44. (2003). Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice.
  45. (2005). T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
  46. (2005). The balance of immune responses: costimulation verse coinhibition.
  47. (1980). The enhancement of humoral and cellular immune responses by dimethyldioctadecylammonium bromide.
  48. (2007). The paradox of CD5-expressing B cells in systemic lupus erythematosus.
  49. (2008). Toll-like receptors in autoimmunity.
  50. (2007). Toll-like receptors: paving the path to T cell-driven autoimmunity?
  51. (2002). Trafficking of CD44-deficient murine lymphocytes under normal and inflammatory conditions.
  52. (1980). Variable expression of delayed hypersensitivity in different mouse strains using dimethyl dioctadecyl ammonium bromide as an adjuvant. Immunology 39:399.

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