CD4+ and CD8+ clonal T cell expansions indicate a role of antigens inankylosing spondylitis; a study in HLA-B27+ monozygotic twins

Clinical and Experimental Immunology - Tập 123 Số 2 - Trang 315-322 - 2001
Rainer Duchmann1, Carsten Lambert2, Ekkehard May2, Thomas Höhler2, E. Märker‐Hermann2
1Internal Medicine II, University of the Saarland, Hamberg and
2Department of Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany

Tóm tắt

SUMMARYAnkylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether the T cell repertoires of individuals with AS show signs of increased stimulation by exogenous antigens, CD4+ and CD8+ T cell subsets of five monozygotic HLA-B27+ twins (two concordant and three discordant for AS) and CD8+ T cell repertoires of three healthy HLA-B27+ individuals were characterized by TCR β-chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR3 spectra were further analysed by BJ-segment analysis and TCRB-CDR3 from expanded T cell clones were sequenced. In an analysis of all data (519/598 possible TCRB-CDR3 spectra), AS was associated with increased T cell oligoclonality in both CD8+ (P = 0·0001) and CD4+ (P = 0·033) T cell subsets. This was also evident when data were compared between individual twins. Nucleotide sequence analysis of expanded CD8+ or CD4+ T cell clones did not show selection for particular TCRB-CDR3 amino acid sequence motifs but displayed sequence homologies with published sequences from intra-epithelial lymphocytes or synovial T cells from rheumatoid arthritis patients. Together, these results provide support for the hypothesis that responses to T cell-stimulating exogenous or endogenous antigens are involved in the induction and/or maintenance of AS.

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