Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis.
OBJECTIVE
To investigate whether T cells in the inflamed joints of patients with rheumatoid arthritis (RA) preferentially produce the T helper 1 (Th1) cytokines, interferon-gamma (IFN gamma) and interleukin-2 (IL-2), or the Th2 cytokine, IL-4, when compared with corresponding peripheral blood-derived T cells.


METHODS
Synovial fluid mononuclear cells (SFMC) and corresponding peripheral blood mononuclear cells (PBMC) from 10 patients with RA were analyzed, either directly or after in vitro stimulation, for the intracellular presence of Th1 and Th2 cytokines. The amount of secreted cytokine in the cell culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
IFN gamma-containing cells were detected in the unstimulated SFMC, but not in the PBMC, of 3 patients with RA. Cells positive for IL-2 or IL-4 were not detected in the unstimulated samples. Following stimulation, the mean percentage of cells containing Th1 cytokines was significantly increased in the SFMC compared with the PBMC; no differences were found in the mean percentage of IL-4-containing cells. A comparable shift toward Th1 cytokines was observed when the amount of secreted cytokine was determined by ELISA.


CONCLUSIONS
A shift toward T cells with a Th1 cytokine profile was observed in the joints of patients with RA. Since an imbalance between Th1 and Th2 cells is thought to be of pathogenic significance, this finding might have implications for the development of new therapies for RA.
Dolhain
R J
RJ
Leiden University Hospital, Department of Rheumatology, The Netherlands.
van der Heiden
A N
AN
ter Haar
N T
NT
Breedveld
F C
FC
Miltenburg
A M
AM
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology*; D017252:CD3 Complex / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma