CD28 expression on T cell subsets in vivo and CD28-mediated T cell response in vitro in patients with rheumatoid arthritis.
OBJECTIVE
In view of the critical importance of the CD28-CD80 (B7/BB1) costimulatory pathway in antigen-specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3-mediated and B7/BB1-costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA).


METHODS
Two-color immunofluorescence analyses of peripheral blood and synovial fluid-derived T cells, as well as 3H-thymidine incorporation assays, were performed.


RESULTS
In the peripheral blood of 31 patients with active, untreated RA, a mean of 91% (range 48-100%) of CD4+ and 46% (range 13-82%) of CD8+ T cell subsets were CD28+, which was not significantly lower than normal. Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower in RA patients (mean 233/microliters, versus 292/microliters in controls), and this decrease was more pronounced in patients with severe disease (mean 172/microliters). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA-DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CD3 monoclonal antibody were identical in patients with RA and healthy individuals.


CONCLUSIONS
Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.
Sfikakis
P P
PP
Athens University School of Medicine, Greece.
Zografou
A
A
Viglis
V
V
Iniotaki-Theodoraki
A
A
Piskontaki
I
I
Tsokos
G C
GC
Sfikakis
P
P
Choremi-Papadopoulou
H
H
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018122:B7-1 Antigen / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology
D018122:B7-1 Antigen; D018106:CD28 Antigens