Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases.
To explore the effects of asbestos and silica on the human immune system, an experimental model of low-dose and long-term exposure was established using a human HTLV-1-immortalized polyclonal T cell line, MT-2 (MT-2Org). MT-2 cells were continuously exposed to asbestos at a concentration (10 microg/ml) which does not induce complete cell death during short-term exposure. After acquiring resistance to CB-induced apoptosis (designated MT-2Rst), an immunological comparison was made between the MT-2Org and MT-2Rst lines in terms of T cell receptor-Vbeta (TcR-Vbeta) expression. MT-2Rst cells showed excess expression of various TcR-Vbeta, although TcR-Vbeta-overpresenting cells were characterized as undergoing apoptosis due to first contact with CB. Patients with asbestos-related diseases (ARD), such as asbestosis and malignant mesothelioma, were compared with silicosis (SIL) patients as a disease control and with healthy donors (HD). SIL and ARD not only differed in their causative materials, silica and asbestos as mineral silicates, but also in terms of complications; autoimmune disorders in SIL and tumors in ARD. ARD patients showed a restricted overpresentation of TcR-Vbeta without clonal expansion, whereas SIL patients revealed significant overpresentation of TcR-Vbeta 7.2. These experimental and clinical analyses indicate the superantigenic and dysregulation of autoimmunity-inducing effects of asbestos and silica, respectively.
Nishimura
Y
Y
Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Miura
Y
Y
Maeda
M
M
Hayashi
H
H
Dong
M
M
Katsuyama
H
H
Tomita
M
M
Hyodoh
F
F
Kusaka
M
M
Uesaka
A
A
Kuribayashi
K
K
Fukuoka
K
K
Nakano
T
T
Kashimoto
T
T
Osuki
T
T
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001194:Asbestos / Q000633:toxicity*; D001195:Asbestosis / Q000276:immunology*; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D001194:Asbestos; D012822:Silicon Dioxide