Virus-induced polyclonal T cell activation is followed by apoptosis: partitioning of CD8+ T cells based on alpha 4 integrin expression.

Virus-induced polyclonal T cell activation is followed by apoptosis: partitioning of CD8+ T cells based on alpha 4 integrin expression.
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病毒诱导的多克隆 T 细胞激活后发生细胞凋亡:根据 α4 整合素表达对 CD8 T 细胞进行分配。

DOI:
10.1093/intimm/8.5.707
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发表时间:
1996
影响因子:
4.4
通讯作者:
A. Thomsen
A. Thomsen
中科院分区:
医学3区
文献类型:
--
作者:
J. Christensen;C. Röpke;A. Thomsen

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淋巴细胞性脉络丛脑膜炎病毒(LCMV)的全身性感染伴有显著的脾肿大,主要反映了具有活化表型(例如VLA-4 hi)的CD 8(+)T细胞的蓄积。使用7-氨基放线菌素-D分析DNA含量显示,多达30%的CD 8(+)T细胞在感染后第6天左右进行循环,并且几乎所有的循环细胞都表达高水平的VLA-4。与相对稳定的CD 4+细胞数量雅阁,仅观察到少量的循环CD 4+细胞。病毒控制后,脾淋巴细胞数量逐渐减少,在此期间,使用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记在白色髓中检测到许多凋亡细胞。DNA含量的流式细胞术分析显示,在CD 8(+)VLA-4 hi亚群中,DNA水平低于正常水平的细胞频率较高,而研究的其他淋巴细胞亚群(CD 4+、CD 8 +VLA-4 lo和B细胞)的频率较低。此外,CD 8 +VLA-4 hi)细胞的数量在应答峰值时占脾细胞的约30%,并且在脾细胞数量正常化期间优先减少。总之,这些发现表明,LCMV诱导的T细胞活化之后是许多活化细胞的凋亡。那些在LCMV免疫小鼠中持续存在的CD 8 +VLA-4 hi细胞对细胞周期特异性药物羟基脲的治疗比表型幼稚T细胞更敏感。因此,我们的研究结果表明,LCMV感染诱导CD 8+细胞的多克隆活化,随后是大多数触发细胞的凋亡,而较小的子集作为包括循环细胞的引发群体持续存在。
Systemic infection with lymphocytic choriomeningitis virus (LCMV) is accompanied by marked splenomegaly, primarily reflecting the accumulation of CD8(+) T cells with an activated phenotype (e.g. VLA-4hi). Analysis of DNA content using 7-aminoactinomycin-D revealed that as many as 30% of CD8(+) T cells are cycling around day 6 post-infection and that virtually all cycling cells express a high level of VLA-4. In accord with the relatively stable CD4+ cell number, only few cycling CD4+ cells were observed. Following virus control, splenic lymphocyte numbers decreased gradually and during this period many apoptotic cells were detected in the white pulp using terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling. Flow cytometric analysis of DNA content revealed a high frequency of cells with subnormal levels of DNA in the CD8(+)VLA-4hi subset, whereas the frequency was low for other lymphocyte subsets studied (CD4+, CD8+VLA-4lo and B cells). In addition, numbers of CD8+VLA-4hi) cells constitute approximately 30% of splenocytes at the peak of the response and undergo preferential decrease during normalization of splenocyte numbers. Together these findings indicate that LCMV-induced activation of T cells is followed by apoptosis of many of the activated cells. Those CD8+VLA-4hi cells which do persist in LCMV immune mice are more sensitive to treatment with the cell-cycle-specific drug hydroxyurea than are phenotypically naive T cells. Our results therefore indicate that LCMV infection induces polyclonal activation of CD8+ cells which is followed by apoptosis of most of the triggered cells while a smaller subset persists as a primed population which include cycling cells.
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DOI: --
发表时间: 1995
期刊: Journal of immunology (Baltimore, Md. : 1950)
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DOI: 10.4049/jimmunol.136.8.2769
发表时间: 1986-04
影响因子: 4.4
作者:
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