Breakdown of self-tolerance by intrathymic injection of a T-cell line inducing autoimmune gastritis in mice.
Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3 days after birth (3d-Tx). We first confirmed our previous observations that CD4+ splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice suppressed the development of the disease. In addition, we found that a quantitative balance between these effector (Te) and suppressor (Ts) T cells determined either onset or prevention of the disease. Peripheralization of Ts seemed to begin around 3 days after birth, since the incidence of AIG in mice that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts existed in the 6d-Tx mice that escaped AIG. We next examined the target specificity of such Ts using syngeneic parietal cells known as autoantigens and two kinds of T-cell lines established from an AIG mouse; one is gastritis inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic injection of parietal cells into mice 3 days after birth followed by 6d-Tx completely prevented the development of AIG. In contrast, injection of irradiated A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune oophoritis (AIO) was induced in female mice, implying that the breakdown of tolerance is organ specific. Taken together, peripheral tolerance for organ-specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which induces the disease.
Nishio
A
A
Institute for Immunology, Faculty of Medicine, Kyoto University, Japan.
Katakai
T
T
Hosono
M
M
Inaba
M
M
Sakai
M
M
Okuma
M
M
Kasakura
S
S
Masuda
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005756:Gastritis / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology