Expression and function of inducible costimulator on peripheral blood T cells in patients with systemic lupus erythematosus.
OBJECTIVE
To investigate the role of inducible costimulator (ICOS) in the pathogenesis of SLE, we assessed its expression on peripheral blood CD4 and CD8 T cells and functional roles in patients with systemic lupus erythematosus (SLE).


METHODS
Expression of ICOS on peripheral blood CD4 and CD8 T cells and ICOS ligand (ICOSL) on peripheral blood CD19 B cells from patients with SLE, patients with rheumatoid arthritis (RA) and healthy volunteers were determined by two-colour flow cytometry. The functional costimulatory effects of ICOS on peripheral blood mononuclear cells (PBMC) were assessed by T-cell proliferative responses, cytokines, anti-double-stranded DNA (anti-dsDNA) antibody and total IgG production.


RESULTS
Peripheral blood CD4 and CD8 T cells expressing ICOS were significantly increased in patients with SLE compared with patients with RA and healthy subjects. Peripheral blood CD19 B cells expressing ICOSL in SLE were markedly reduced compared with RA. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher than those of anti-CD3/hamster IgG (HIgG) in healthy subjects, but not in patients with SLE. Anti-CD3/ICOS-stimulated SLE PBMC secreted similar levels of IL-10 and IFN-gamma but a significantly lower level of IL-2 than healthy PBMC. Anti-CD3/ICOS-mediated costimulation significantly enhanced the production of anti-dsDNA antibodies and total IgG in patients with SLE.


CONCLUSIONS
Hyperexpression of ICOS on peripheral blood CD4 and CD8 T cells from patients with SLE contributed to the dysregulated T-cell proliferation, T-cell activation and pathogenic autoantibody production, which showed that the abnormality of ICOS costimulation may play an immunopathological role(s) in the pathogenesis of SLE.
Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, P. R. China.
Jia-Hui
JH
Yang
Jun
J
Zhang
Qing
Q
Cai
Dang-Bao
DB
Zhao
Jian
J
Wang
Ping-E
PE
Guo
Li
L
Liu
Xing-Hai
XH
Han
Qian
Q
Shen
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D000974:Antibodies, Antinuclear; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556692:ICOS protein, human; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D004247:DNA