Shift toward T helper 1 cytokines by type II collagen-reactive T cells in patients with rheumatoid arthritis.
OBJECTIVE
To investigate the impact of type II collagen (CII)-reactive T cells on the Th1/Th2 cytokine balance in patients with rheumatoid arthritis (RA).


METHODS
T cell proliferative responses to bovine CII were examined in synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) by mixed lymphocyte culture. CII-reactive T cell lines were generated from the SFMC and PBMC. Interferon-gamma (IFNgamma), interleukin-12 (IL-12), and IL-4 were measured by enzyme-linked immunosorbent assay in the SF, sera, and culture supernatants of PBMC and SFMC that had been stimulated with CII.


RESULTS
The frequency of CII-reactive T cells was higher in the PBMC from RA patients than in that from osteoarthritis patients and healthy control subjects. In RA patients, CII-reactive T cells were more prevalent in SFMC than in PBMC. The mean level of IFNgamma and the ratio of IFNgamma to IL-4 were significantly higher in the culture supernatants of T cells stimulated with CII; these differences were more prominent in SFMC. Levels of IL-12 in the culture supernatants of SFMC and PBMC stimulated with CII were significantly higher than those in unstimulated supernatants. T cell responsiveness correlated well with the level of type 1 cytokines in culture supernatants from RA T cells stimulated with CII. In the CII-reactive cell lines, the increased production of IFNgamma was consistent with clonal expansion.


CONCLUSIONS
CII-reactive T cells are more abundant in SFMC than in PBMC and are strongly associated with a shift toward Thl cytokine in the inflamed joints of RA patients. Our results suggest that a skewing toward type 1 cytokines by CII-reactive T cells may play an important role in the chronic inflammatory process of RA.
Park
S H
SH
Catholic University of Korea, Seoul.
Min
D J
DJ
Cho
M L
ML
Kim
W U
WU
Youn
J
J
Park
W
W
Cho
C S
CS
Kim
H Y
HY
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology*; D003094:Collagen / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000473:pathology; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*; D018417:Th1 Cells / Q000378:metabolism*
D016207:Cytokines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen