CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis.
CD4(+) CD25(+) regulatory T (T(reg)) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4(+) CD25(+) T(reg) cells in patients with rheumatoid arthritis (RA). The frequency and phenotype of CD4(+) CD25(+) T cells in paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with RA and PB from normal controls were analysed. An increased frequency of CD4+ cells T cells expressing CD25 was detected in SF compared to PB from patients with RA. No significant difference was observed in the numbers of CD4(+) CD25(+) T cells in PB from patients and controls. SF CD4(+) CD25(+) T cells expressed high levels of CTLA-4 (both surface and intracellular), GITR and OX40, as well as Foxp3 transcripts. Functionally, SF CD4(+) CD25(+) T cells were impaired in their proliferative responses and could suppress the proliferation of their CD4(+) CD25(-) counterparts. In conclusion, these data demonstrate that CD4(+) CD25(+) T(reg) cells, with the potential to regulate the function of effector T cells and antigen-presenting cells, accumulate in the synovium of patients with RA.
Möttönen
M
M
Turku Graduate School of Biomedical Sciences, Turku, Finland. nilja.mottonen@utu.fi
Heikkinen
J
J
Mustonen
L
L
Isomäki
P
P
Luukkainen
R
R
Lassila
O
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013582:Synovial Fluid / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2