Expression and function of the co-stimulator H4/ICOS on activated T cells of patients with rheumatoid arthritis.
OBJECTIVE
To investigate the expression and function of the inducible co-stimulator H4/ICOS in rheumatoid arthritis (RA) patients. H4/ICOS is the newest member of the CD28/CTLA-4 family to have been found to be expressed on activated T cells, and it participates in a variety of important immunoregulatory functions.


METHODS
The levels of H4/ICOS expression on T cells among peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from 28 patients with RA were analyzed by flow cytometry. To explore the role of H4/ICOS function in the inflammation of rheumatoid joints, lymphokine production by SF CD4+ T cells co-stimulated by H4/ICOS was assayed. Expression of H4/ICOS ligand (B7RP-1) mRNA in synovial tissues from patients with RA was examined by reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
H4/ICOS-positive cells were increased significantly in whole, CD4+, and CD8+ T-cell fractions of SFMC compared with control PBMC. Comparison between control PB and PB from patients with active RA showed that H4/ICOS-positive whole and CD8+ T-cell fractions were increased significantly in the PB of RA patients. H4/ICOS costimulation clearly increased interferon-g, interleukin 4 (IL-4), and IL-10 production by SF CD4+ T cells. By RT-PCR, RA synovial tissue was shown to express mRNA of B7RP-1.


CONCLUSIONS
Our results suggest that local immune responses may be modulated by H4/ICOS expressed on T cells in the joints of patients with RA, and thus H4/ICOS may be involved in the pathogenetic mechanism of RA.
Okamoto
Toshihiro
T
Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, Japan. okamoto@oms.twmu.ac.jp
Saito
Seiji
S
Yamanaka
Hisashi
H
Tomatsu
Taisuke
T
Kamatani
Naoyuki
N
Ogiuchi
Hideki
H
Uchiyama
Takehiko
T
Yagi
Junji
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D007596:Joints / Q000276:immunology; D008024:Ligands; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D008222:Lymphokines