An in vitro model for cyclosporin A-induced interference of intrathymic clonal elimination.
The effects of cyclosporin A (CsA) on influencing the intrathymic clonal deletion were investigated by using our established thymic stromal cell clone with capacities to express Ia antigens and to produce a unique T cell growth factor. The following were revealed: (a) T cell clone with a given specificity was killed on the Ia+ stromal cell monolayer in the presence of the relevant antigens, a process depending on T cell receptor (TCR) stimulation; and (b) CsA allowed the T cell clone to continuously proliferate even during TCR stimulation by virtue of the stromal cell-derived T cell growth factor. This paper describes an in vitro model of a mechanism by which CsA is responsible for the generation of normally "forbidden" T cell clones.
Kosaka
H
H
Biomedical Research Center, Osaka University Medical School, Japan.
Matsubara
H
H
Sogoh
S
S
Ogata
M
M
Hamaoka
T
T
Fujiwara
H
H
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D003524:Cyclosporins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000187:drug effects; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D003524:Cyclosporins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D007371:Interferon-gamma