Defective signal transduction via T-cell receptor-CD3 structure in T cells from rheumatoid arthritis patients.
T cells from patients with active RA are known to produce low levels of IL-2 and proliferate poorly in response to various mitogenic stimuli. The present work shows that cross-linking of CD3 antigen on patients' T-cell surface induces two- to threefold lower Ca2+ response than in T cells from age-matched controls. Immunofluorescence studies indicate that the attenuated signal may be due to the suppressed expression of CD3 and/or CD45 molecules on patients' T cells. In the majority of the patients, the level of CD45 expression is reduced by 60%-70% as compared with that in the control T cells. Therefore, the poor mitogenic response of patient cells is apparently due to a defect in early stages of signal transduction through the T-cell receptor (TCR-CD3).
Mirza
N M
NM
Division of Immunogenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Relias
V
V
Yunis
E J
EJ
Pachas
W N
WN
Dasgupta
J D
JD
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D007165:Immunosuppression Therapy; D007211:Indoles / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D016853:Muromonab-CD3 / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D005456:Fluorescent Dyes; D007211:Indoles; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D017493:Leukocyte Common Antigens; D015232:Dinoprostone; C048960:indo-1; D002118:Calcium