Oligoclonal CD4+ CD57+ T-cell expansions contribute to the imbalanced T-cell receptor repertoire of rheumatoid arthritis patients.
A peculiar feature of rheumatoid arthritis patients is that they carry clonally expanded CD4+ and CD8+ cells in the peripheral blood. While the distortion of the repertoire of CD8+ cells has been ascribed to the increase of CD8+ CD57+ large granular lymphocytes, often detected in these patients, the mechanism responsible for the clonal expansion of CD4+ cells remains unexplained. Here, we report that CD4+ CD57+ cells, that in healthy individuals represent a small subset of peripheral CD4+ lymphocytes, are significantly expanded in the peripheral blood of a considerable percentage of rheumatoid arthritis patients. Furthermore, the expansion of these lymphocytes appears to correlate with the presence of rheumatoid factor. The molecular analysis of the T-cell receptor variable beta segments expressed by the CD4+ CD57+ cells enriched in rheumatoid arthritis patients showed that they use restricted repertoires, that partially overlap with those of their CD4- CD57+ counterpart. The structural feature of the receptor ligand expressed by these cells revealed that their expansion is most likely mediated by strong antigenic pressures. However, since we also found that CD4+ CD57+ and CD4- CD57+ cells can share the same clonal specificity, it is likely that their selection is not mediated by conventional major histocompatibility complex restricted mechanisms. Thus, while our data demonstrate that CD4+ CD57+ cells play an important role in establishing the imbalance of the CD4+ cell repertoire observed in rheumatoid arthritis patients, they also suggest that these cells have common features with mouse CD4+ CD8- NK1.1+/T cells.
Imberti
L
L
Consorzio per le Biotecnologie, Terzo Laboratorio Analisi, Clinic Immunology Department, Spedali Civili, Brescia, Italy.
Sottini
A
A
Signorini
S
S
Gorla
R
R
Primi
D
D
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D018959:CD57 Antigens / Q000032:analysis; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D016415:Sequence Alignment; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015704:CD4 Antigens; D018959:CD57 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta