CD4+ and CD8+ clonal T cell expansions indicate a role of antigens in ankylosing 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 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 beta-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.
Duchmann
R
R
Internal Medicine II, University of the Saarland, Hamberg. inrduc2med-rz.uni-sb.de
Lambert
C
C
May
E
E
Höhler
T
T
Märker-Hermann
E
E
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014427:Twins
D015796:HLA-B27 Antigen; D011948:Receptors, Antigen, T-Cell