Selection of T cells reactive against autologous B lymphoblastoid cells during chronic rheumatoid arthritis.
The repertoire and Ag specificity of T cells infiltrating inflamed joints from a chronic rheumatoid arthritis (RA) patient were studied in detail. Repertoire analysis demonstrated a reduced clonality of joint-infiltrating lymphocytes (JIL) as compared with patient's PBL, which was presumably due to an intra-articular expansion of T cell clones with recurrent TCR features. Strikingly, a large fraction of these JIL T cell clones, which were predominantly CD8+, proliferated in vitro when exposed to autologous B lymphoblastoid cells (BLC), unlike randomly chosen PBL clones derived from the same patient. This proliferative response was HLA-restricted, which confirmed a classical TCR-mediated recognition of BLC and was not observed against autologous PHA blasts, suggesting recognition of either EBV or B cell-specific Ags. Finally, a preliminary analysis of synovial lymphocytes derived from another chronic RA patient demonstrated a similar enrichment for T cells reactive against autologous BLC within JILs as compared with patient's PBLs. Taken together, these results, which suggest frequent expansions of autologous BLC-reactive T cells within inflamed joints of chronic RA patients, provide a basis for future studies evaluating the fine specificity and pathogenicity of these lymphocytes.
INSERM Unit 211, Institute of Biology, Nantes, France.
J
J
David-Ameline
A
A
Lim
F
F
Davodeau
M A
MA
Peyrat
J M
JM
Berthelot
G
G
Semana
C
C
Pannetier
J
J
Gaschet
H
H
Vie
J
J
Even
M
M
Bonneville
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D002908:Chronic Disease; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007596:Joints; D008213:Lymphocyte Activation; D005810:Multigene Family / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta