title: Immunization with TCR Vbeta10 peptide reduces the frequency of type-II collagen-specific Th1 type T cells in BUB/BnJ (H-2q) mice.
abstract: OBJECTIVE
  Collagen induced arthritis (CIA) in mice is mediated by synergistic T cell and humoral immune responses specific for type II collagen (CII). We have previously shown that in arthritic joints of BUB mice (TCR Vbetaa, H-2q) the TCR repertoire is enrichedfor Vbeta10 expressing T cells, and that immunization with a Vbeta10 peptide (Vbeta10p) prevents the phenotypic expression of disease. The objective of the present study was to understand how immunization with a synthetic TCR Vbeta peptide affected the development of the pathogenic CII-specific immune response in BUB mice.
  
  
  METHODS
  Arthritic and protected animals were tested for Vbeta10p- and CII-specific cytokine production by a highly specific and sensitive ELISA spot assay, andfor CII-specific antibody production by standard ELISA. In adoptive transfer experiments, Vbeta10p-specific LN cells (INF-gamma producing) were injected into naive mice prior to immunization with type-II collagen/CFA.
  
  
  RESULTS
  Immune cells from arthritic animals produced IFN-gamma and IL-2, without IL-4 and IL-5 in response to CII and an immunodominant epitope, A2, derivedfrom CII. Serum from these mice contained anti-CII antibodies of both IgGI and IgG2a subtypes. Our results show for thefirst time that immunization with Vbeta10p resulted in Vbeta10p-specific IFN-gamma and IL-2 production that was restricted to the CD4+ T cell subset. Emergence of this Vbeta10p-specific immune response was associated with a dramatic decrease in the frequency of CII and A2-specific, cytokine producing T cells in arthritis protected mice. Protective immunity was cell mediated and could be adoptively transferred. In contrast, the protective immunization had only a marginal effect on the anti-CII antibody response indicating that the CII specific humoral immune response was not significantly affected.
  
  
  CONCLUSIONS
  Immunization with TCR Vbeta10p leads to expansion of a population of Vbeta10p- specific CD4+ Tcells. This anti-TCR Vbeta10p specific type 1 cytokine producing immune response was protective in adoptive transfer studies and appears to inhibit the expansion of the pathogenic anti-CII cellular immunity. Additionally, the anti-TCR Vbeta10p-specific cellular immune response was mediated by CD4+ T cells and these T cells did not produce IL-4 or IL-5. Thus, our results suggest that protection against CIA in mice immunized with synthetic TCR Vbeta10p was achieved by a specific down-regulation of the CII-specific Thl type cellular immune response and not via immune deviation.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland OH 44106-4946, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Anthony
authors.forename: P S
authors.initials: PS
authors.lastname: Heeger
authors.forename: T M
authors.initials: TM
authors.lastname: Haqqi
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D024043:Collagen Type II / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016059:Range of Motion, Articular; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta