HIV type 1-induced inhibition of CD45 tyrosine phosphatase activity correlates with disease progression and apoptosis, but not with anti-CD3-induced T cell proliferation.
HIV type 1-induced inhibition of CD45 tyrosine phosphatase activity correlates with disease progression and apoptosis, but not with anti-CD3-induced T cell proliferation.
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HIV 1 型诱导的 CD45 酪氨酸磷酸酶活性抑制与疾病进展和细胞凋亡相关，但与抗 CD3 诱导的 T 细胞增殖无关。
DOI：
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发表时间：
2000
影响因子：
1.5
通讯作者：
F. Aiuti
中科院分区：
文献类型：
--
作者：
A. Giovannetti;M. Pierdominici;F. Mazzetta;A. Mazzone;G. Ricci;A. Prozzo;F. Pandolfi;R. Paganelli;F. Aiuti
酪氨酸磷酸酶CD 45是多个淋巴细胞信号传导途径中的关键阳性元件。为了了解CD 45对HIV-1诱导的T细胞低反应性和细胞凋亡的作用，我们评估了来自不同阶段HIV-1疾病患者的淋巴细胞的CD 45相关酪氨酸磷酸酶活性，并将其与CD 45表达、自发和Fas诱导的细胞凋亡、抗CD 3诱导的T细胞增殖、CCR 5 δ 32/wt分布和细胞因子产生进行比较。抗CD 3增殖反应以及CD 45相关的磷酸酶活性显着降低进展。在长期无进展者（LTNP）中，抗CD 3的增殖反应也减弱，尽管程度较小，而酪氨酸磷酸酶活性未显著受损。三分之一的LTNP被发现CCR 5基因的32-bp缺失呈阳性。该突变对抗CD 3增殖反应或CD 45磷酸酶活性没有影响。在LTNP和正常进展者中均观察到IL-2和IFN-γ的显着减少，而IL-4的产生仅在进展者中显着减少。最后，我们观察到CD 45磷酸酶活性与细胞凋亡之间的显著相关性。因此，我们得出结论，CD 45酪氨酸磷酸酶活性的损害与疾病的进展和T细胞凋亡的水平，但不与抗CD 3诱导的T细胞增殖。此外，我们认为，CD 45酪氨酸磷酸酶活性的评价可能是一个额外的工具，以评估疾病的进展。
The tyrosine phosphatase CD45 is a key positive element in multiple lymphocyte signaling pathways. To understand the contribution of CD45 to HIV-1-induced T cell hyporesponsiveness and apoptosis we evaluated the CD45-associated tyrosine phosphatase activity of lymphocytes from patients with different stages of HIV-1 disease and compared it with CD45 expression, spontaneous and Fas-induced apoptosis, anti-CD3-induced T cell proliferation, distribution of CCR5 delta32/wt, and cytokine production. The proliferative response to anti-CD3 as well as the CD45-associated phosphatase activity were significantly reduced in progressors. In long-term nonprogressors (LTNPs) the proliferative response to anti-CD3 was also diminished, although to a lesser extent, while the tyrosine phosphatase activity was not significantly impaired. One-third of LTNPs were found positive for the 32-bp deletion of the CCR5 gene. This mutation had no effects on anti-CD3 proliferative response or CD45 phosphatase activity. A significant reduction in IL-2 and IFN-gamma was observed in both LTNPs and in normal progressors, whereas IL-4 production was significantly decreased only in progressors. Last, we observed a significant correlation between CD45 phosphatase activity and apoptosis. We therefore conclude that the impairment of CD45 tyrosine phosphatase activity correlates with disease progression and the level of T cell apoptosis, but not with anti-CD3-induced T cell proliferation. Moreover, we suggest that evaluation of CD45 tyrosine phosphatase activity may represent an additional tool with which to assess disease progression.
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DOI：
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发表时间：
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DOI：
10.1073/pnas.93.20.11014
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