Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.
Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.
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胸腺内 T 细胞前体及其携带 T 细胞抗原受体表型 TCR α β 和 TCR γ δ 的后代对人类免疫缺陷病毒感染易感性的证据：CD4 (T4) 淋巴细胞耗竭的机制。
DOI：
10.1073/pnas.87.19.7727
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发表时间：
1990
影响因子：
11.1
通讯作者：
Fauci,AS
中科院分区：
文献类型：
--
作者：
Schnittman,SM;Denning,SM;Greenhouse,JJ;Justement,JS;Baseler,M;Kurtzberg,J;Haynes,BF;Fauci,AS
感染人类免疫缺陷病毒1型（HIV-1）的个体表现出辅助性T4（CD 4+）细胞群的进行性耗竭和定性功能障碍。提出的CD 4 + T细胞消耗的机制包括这些成熟细胞在感染后的直接细胞病变以及早期T淋巴细胞祖细胞的感染。后一种机制可能导致无法再生成熟的功能性CD 4 + T细胞。本研究确定了胸腺细胞在不同成熟阶段对HIV-1感染的易感性。用HIV-1接种各种正常胸腺细胞群，包括未分级（UF）、CD 3-CD 4-CD 8- [“三阴性”（TN）]、CD 4 + CD 8 + [“双阳性”（DP）]胸腺细胞和通过有限稀释克隆获得的胸腺细胞群。除了检测逆转录酶活性外，还通过聚合酶链反应研究了培养物中是否存在HIV-1 DNA。我们确定完全缺乏CD 4的转化T细胞和胸腺细胞系对HIV-1感染不敏感，而以下所有细胞系均为：（70-90% CD 4 hi+）; DP胸腺细胞（99% CD 4 hi+）; TN胸腺细胞（0%CD4hi+）;和表达可变水平的CD 4并代表TN胸腺细胞后代的TCR α β +、TCR γ δ +或CD 16 + CD 3-（自然杀伤）胸腺细胞克隆。[TCRα β +和TCR γ δ +是指T细胞抗原受体（TCR）的链，而CD 4 hi是指与对照相比，在流式细胞术分析中CD 4曲线的强烈的红移（大于30个线性通道）。]抗CD 4（T4 a表位）的单克隆抗体（mAb）能够阻断成熟和未成熟的CD 4 hi+胸腺细胞的感染，但不能阻断CD 3（T3）。此外，抗CD 4（T4 a）单克隆抗体也抑制了CD 4 hi-TN胸腺细胞的感染，表明这些T细胞前体-尽管它们具有明显的“三阴性”（CD 3-CD 4 hi-CD 8-）-表达了足够的CD 4分子，从而被感染。用一组CD 4 mAb进行的细胞分选仪分析表明，在TN胸腺细胞上用CD 4 mAb进行的平均荧光通道（MFC）的平均偏移为6 +/-4 MFC单位。因此，胸腺内T细胞前体及其后代代表T细胞个体发育的许多阶段，易受HIV-1感染，包括早期TN胸腺细胞，其表达非常低水平的CD 4。通过CD 4分子介导的人类T细胞谱系的多个阶段和多个亚群的感染可以解释T细胞库在进行性HIV感染的情况下不能再生。
Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors. The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells. The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1. Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- ["triple negative" (TN)], CD4+ CD8+ ["double positive" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning. Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity. We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes. [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes. Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent "triple negativity" (CD3- CD4hi- CD8-)--expressed sufficient CD4 molecules to become infected. Cell sorter analysis with a panel of CD4 mAbs demonstrated a mean shift of the mean fluorescence channel (MFC) with CD4 mAbs on TN thymocytes of 6 +/- 4 MFC units. Thus, intrathymic T-cell precursors and their progeny representing many stages of T-cell ontogeny are susceptible to infection by HIV-1, including early TN thymocytes, which express very low levels of CD4. Infection of multiple stages and multiple subsets of the T-cell lineage in man, mediated via the CD4 molecule, may explain the inability of the T-cell pool to regenerate in the setting of progressive HIV infection.
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获得性免疫缺陷综合征中，胸腺退化早熟表现为上皮损伤。
影响因子：
3.3
作者：
T. Seemayer;A. Laroche;P. Russo;R. Malebranche;E. Arnoux;J. Guerin;G. Pierre;J. Dupuy;J. Gartner;W. Lapp
通讯作者：
W. Lapp
DOI：
10.4049/jimmunol.142.9.2988
发表时间：
1986
期刊：
The American journal of pathology
影响因子：
--
作者：
W. Savino;M. Dardenne;C. Marche;D. Trophilme;J. Dupuy;D. Pekovic;N. Lapointe;J. Bach
通讯作者：
J. Bach
人类逆转录病毒 HTLV-III/LAV 的细胞趋向性。
影响因子：
4.4
作者：
J. Mcdougal;A. Mawle;S. Cort;J. Nicholson;G. Cross;J. A. Scheppler;D. Hicks;J. Sligh
通讯作者：
J. Sligh
人出生后 CD4-CD8-CD3-胸腺 T 细胞前体在体外分化为带有 δ 受体的 T 细胞细胞。
DOI：
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发表时间：
1989
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Denning,SM;Kurtzberg,J;Leslie,DS;Haynes,BF
通讯作者：
Haynes,BF
楠川，N.；尤拉，T.：基因与发育。 2. 874-882 (1988)
DOI：
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发表时间：
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期刊：
影响因子：
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