Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis

Int Immunol. 2001 Dec;13(12):1541-50. doi: 10.1093/intimm/13.12.1541.

Abstract

Clinically distinct forms of childhood arthritis are associated with different risk alleles of polymorphic loci within the MHC, which code for the antigen-presenting class I or class II molecules. We have compared the TCR diversity of synovial T cells from children with enthesitis-related (HLA-B27(+)) arthritis and oligoarticular arthritis (with class II MHC risk allele associations) in parallel with peripheral blood T cells from each child, using a high-resolution heteroduplex TCR analysis. We demonstrate that multiple clonal T cell expansions are present and persistent within the joint in both groups, but that there is disease-specific divergence in the dominant T cell subset containing these expansions. Thus, the largest clonotypes within the inflamed joints of children with class II-associated arthritis are within the CD4(+) synovial T cell population, while the dominant clones from children with enthesitis-related arthritis (associated with a class I allele) are within the CD8(+) synovial T cell population. These data provide powerful data to support the concept that recognition of MHC-peptide complexes by T cells plays a role in the pathogenesis of juvenile arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Amino Acid Sequence
  • Arthritis, Juvenile / classification
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Arthritis, Juvenile / pathology*
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cartilage, Articular / immunology
  • Cartilage, Articular / pathology
  • Cell Division / genetics
  • Cell Division / immunology
  • Child
  • Clone Cells
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genetic Predisposition to Disease*
  • HLA Antigens / genetics*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Risk Factors
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*

Substances

  • HLA Antigens
  • Receptors, Antigen, T-Cell, alpha-beta