Capacity of simian virus 40 T antigen to induce self-tolerance but not immunological privilege in the anterior chamber of the eye.

Capacity of simian virus 40 T antigen to induce self-tolerance but not immunological privilege in the anterior chamber of the eye.
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猿猴病毒 40 T 抗原诱导自我耐受的能力,但不诱导眼前房的免疫特权。

DOI:
10.1097/00007890-199403150-00014
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发表时间:
1994
期刊:
影响因子:
6.2
通讯作者:
Niederkorn,JY
Niederkorn,JY
中科院分区:
医学2区
文献类型:
--
作者:
Ma,D;Comerford,S;Bellingham,D;Sambrook,J;Gething,MJ;Alizadeh,H;Anand,R;Mellon,J;Niederkorn,JY

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携带类人猿病毒40 (SV40)大T癌基因的转基因小鼠出现了逐渐生长的眼内肿瘤,并表现出对SV40 T抗原的免疫耐受特征。转基因小鼠对来自转基因眼内肿瘤的携带sv40t抗原的肿瘤细胞系不能产生CTL反应。来自转基因宿主的脾脏细胞能够阻止正常同基因FVB/N小鼠淋巴细胞在体内和体外产生CTL反应。从耐受性转基因供体过继移植脾脏细胞暂时抑制SV40 T抗原阳性肿瘤细胞移植到正常同基因FVB/N受体的免疫排斥反应。因此,将SV40转化序列导入小鼠种系诱导了对SV40 T抗原的耐受性。然而,在正常的FVB/N小鼠中,携带SV40 T抗原的肿瘤细胞在前房没有经历免疫特权,也没有引起系统性的延迟型超敏反应的下调,这种反应通常发生在抗原被引入前房时。结果表明,在眼前房内,宿主免疫系统对携带SV40 T抗原的细胞的感知与其他类型的抗原有很大不同。因此,将SV40 T抗原基因导入宿主种系后,SV40 T抗原可有效诱导自身免疫耐受,但在正常宿主眼前房中却无法获得免疫特权。
Transgenic mice bearing the simian virus 40 (SV40) large T oncogene developed progressively growing intraocular tumors and displayed characteristics of immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL responses to SV40 T antigen-bearing tumor cell lines derived from the transgenic intraocular tumors. Spleen cells from transgenic hosts were able to prevent the in vivo and in vitro generation of CTL responses by lymphocytes from normal syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic donors temporarily inhibited the immunological rejection of SV40 T antigen-positive tumor cells transplanted to normal syngeneic FVB/N recipients. Thus, introduction of SV40 transforming sequences into the mouse germline induced tolerance to SV40 T antigen. However, in normal FVB/N mice, SV40 T antigen-bearing tumor cells failed to experience immune privilege in the anterior chamber and did not elicit systemic down-regulation of delayed-type hypersensitivity responses that characteristically occur when antigens are introduced into the anterior chamber. The results indicate that within the anterior chamber of the eye, SV40 T antigen-bearing cells are perceived by the host's immune system much differently than are other categories of antigen. Thus, SV40 T antigen effectively induces self-immunological tolerance when its gene is introduced into the host's germline but fails to experience immunological privilege in the anterior chamber of the eye in normal hosts.