Immunization with TCR Vβ10 peptide reduces the frequency of type-II collagen-specific Th1 type T cells in BUB/BnJ (H-2q) mice

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 Vβ^a, H-2^q) the TCR repertoire is enriched for Vβ10 expressing T cells, and that immunization with a Vβ10 peptide (Vβ10p) prevents the phenotypic expression of disease. The objective of the present study was to understand how immunization with a synthetic TCR Vβ peptide affected the development of the pathogenic CII-specific immune response in BUB mice. Methods. Arthritic and protected animals were tested for Vβ10p- and CII-specific cytokine production by a highly specific and sensitive ELISA spot assay, and for CII-specific antibody production by standard ELISA. In adoptive transfer experiments, Vβ10p-specific LN cells (INF-γ producing) were injected into naive mice prior to immunization with type-II collagen/CFA. Results. Immune cells from arthritic animals produced IFN-γ and IL-2, without IL-4 and IL-5 in response to CII and an immunodominant epitope, A2, derived from CII. Serum from these mice contained anti-CII antibodies of both IgG1 and IgG2a subtypes. Our results show for the first time that immunization with Vβ10p-specific IFN-γ and IL-2 production that was restricted to the CD4+ T cell subset. Emergence of this Vβ10p-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. Conclusion. Immunization with TCR Vβ10p leads to expansion of a population of Vβ10p- specific CD4+ T cells. This anti-TCR Vβ10p 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 Vβ10p-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 Vβ10p was achieved by a specific down-regulation of the CII-specific Th1 type cellular immune response and not via immune deviation.