Selection of T lymphocytes in two rheumatoid arthritis patients defines different T-cell receptor V beta repertoires in CD4+ and CD8+ T-cell subsets.
To study the selective pressures responsible for the expansion of T cells in rheumatoid arthritis, we constructed cDNA mini-libraries from purified CD4+ and CD8+ T cells prepared from peripheral blood and from synovial fluids of two rheumatoid arthritis patients. Comparison of these libraries by hybridization with specific probes indicated that V beta 2 and V beta 8 transcripts are selectively enriched in the CD4+ synovial fluid lymphocyte population, while V beta 4 was over-represented among both the CD4+ and CD8+ subsets. The enrichment of V beta 14 and V beta 17 observed in synovial fluid T cells of one patient was, however, selectively confined to the CD8+ T-cell subpopulation. Sequence analysis of several V beta 2, V beta 4 and V beta 8 clones, derived from CD4+ cells, revealed a high degree of heterogeneity in the V beta-D beta-J beta junctions, while a more biased utilization of J segments and a more restricted junctional heterogeneity were observed in V beta 4, V beta 14 and V beta 17 clones derived from CD8+ cells. These data suggest that the disease may be induced by the initial activation of a rather heterogeneous population of T-helper cells that are later responsible for the expansion of a more restricted pool of highly specific effector lymphocytes.
Sottini
A
A
Consorzio per le Biotecnologie-Consiglio Nazionale delle Ricerche (CNR), Medical School, Brescia, Italy.
Imberti
L
L
Bettinardi
A
A
Mazza
C
C
Gorla
R
R
Primi
D
D
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013582:Synovial Fluid / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta