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

Ankylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether th e T cell repertoires of individuals with AS show signs of increased stimula tion by exogenous antigens, CD4(+) and CD8(+) T cell subsets of five monozy gotic HLA-B27(+) twins (two concordant and three discordant for AS) and CD8 (+) T cell repertoires of three healthy HLA-B27(+) individuals were charact erized by TCR beta -chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR 3 spectra were further analysed by BJ-segment analysis and TCRB-CDR3 from e xpanded T cell clones were sequenced. In an analysis of all data (519/598 p ossible TCRB-CDR3 spectra), AS was associated with increased T cell oligocl onality 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. Nuc leotide sequence analysis of expanded CD8(+) or CD4(+) T cell clones did no t show selection for particular TCRB-CDR3 amino acid sequence motifs but di splayed sequence homologies with published sequences from intra-epithelial lymphocytes or synovial T cells from rheumatoid arthritis patients. Togethe r, these results provide support for the hypothesis that responses to T cel l-stimulating exogenous or endogenous antigens are involved in the inductio n and/or maintenance of AS.