Peripheral T lymphocyte depletion by apoptosis after CD4 ligation in vivo: selective loss of CD44− and ‘activating’ memory T cells
Peripheral T lymphocyte depletion by apoptosis after CD4 ligation in vivo: selective loss of CD44− and ‘activating’ memory T cells
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体内 CD4 连接后细胞凋亡导致外周 T 淋巴细胞耗竭：选择性损失 CD44− 并“激活”记忆 T 细胞
DOI：
10.1111/j.1365-2249.1994.tb06036.x
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发表时间：
1994
影响因子：
4.6
通讯作者：
D. Harrison
中科院分区：
文献类型：
--
作者：
S. Howie;A. J. Sommerfield;E. Gray;D. Harrison
我们已经证明，单次静脉推注大鼠抗 CD4 MoAb 会导致小鼠淋巴结细胞凋亡小幅但长期增加。我们使用新型高度优化显微镜环境 (HOME) 交互式图像分析系统量化了这一过程，并表明细胞凋亡的增加足以解释所观察到的外周 CD4+ T 细胞亚群的描述。这是在没有任何其他外源信号的情况下发生的。此外，没有证据表明组织出现炎症或坏死反应，表明这不太可能是 He 或补体介导的抗体杀伤。抗 CD4 诱导的描述选择性地去除了 CD44− T 细胞。使用先前用酵母衍生的 HIV-1 p24 重组蛋白免疫的小鼠，在体内抗 CD4 治疗后，记忆 T 细胞功能得到保留，但在少于 24 小时的时间内，同时暴露于抗原和抗 CD4 抗体会导致特定记忆 T 淋巴细胞功能的描述。这表明，随着时间的推移，细胞凋亡频率的微小变化对细胞数量产生显着影响，并表明与 CD4+ T 细胞耗竭相关的机会性感染可能是由于在 CD4 连接的同时存在抗原刺激时记忆细胞的损失所致。这些结果对 HIV 相关疾病的病理学具有影响，该疾病与体内 CD4 分子的连接有关。
We have demonstrated that a single intravenous bolus of rat anti‐CD4 MoAb caused a small but prolonged increase in apoptosis in murine lymph nodes. We have quantified this process using the novel Highly Optimized Microscope Environment (HOME) interactive image analysis system and shown that the increase in apoptosis was sufficient to account for the observed depiction of the peripheral CD4+ T cell subset. This occurred in the absence of any other exogenous signal. Furthermore, there was no evidence of an inflammatory or necrotic response in the tissues, indicating that this was unlikely to be He or complement‐mediated antibody killing. The anti‐CD4‐induced depiction selectively removed CD44− T cells. Using mice previously immunized with yeast‐derived HIV‐1 p24 recombinant protein there was sparing of memory T cell function after in vivo anti‐CD4 treatment, except during a window of less than 24 h duration, when simultaneous exposure to antigen and anti‐CD4 antibody resulted in the depiction of specific memory T lymphocyte function. This indicated that a very minor alteration in the frequency of apoptosis had a marked effect on cell number over time, and suggested that opportunistic infection associated with CD4+ T cell depletion may be explained by loss of memory cells when there is antigenic stimulation at the same time as CD4 ligation. These results have implications for the pathology of HIV‐associated disease which is associated with ligation of CD4 molecules in vivo.