Valentin H, Nugeyre M T, Vuillier F, Boumsell L, Schmid M, Barré-Sinoussi F, Pereira R A
Unité de Biologie des Rétrovirus, Institut Pasteur, Paris, France.
J Virol. 1994 May;68(5):3041-50. doi: 10.1128/JVI.68.5.3041-3050.1994.
Some infants infected with human immunodeficiency virus type 1 (HIV-1) rapidly develop a fatal disease characterized by a severe lymphopenia. To explain the immune dysfunction, we proposed a mechanism by which a nongeneration of CD4+ T cells is caused by HIV-1 infection of thymic cells. To examine this hypothesis, we infected primary triple-negative (TN; phenotypically CD3- CD4- CD8-), CD1a- TN, or CD1a+ TN thymic cell subsets. Our data indicate that by flow cytometry, TN, CD1a- TN, and CD1a+ TN cells remain CD4 negative throughout the culture period. We demonstrated that TN and CD1a+ TN thymic cell subsets are susceptible to HIV-1 as is the entire thymic cell population, whereas CD1a- TN cells are not. A limited number of infected TN cells are expressing HIV-1 but the level of transcription is very high in permissive cells, as detected by in situ hybridization. We then performed blocking experiments on TN cells to examine the mechanism of HIV-1 entry into these cells. CD4 (OKT4a) monoclonal antibody blocks their infection. Finally, infection experiments on two subpopulations of TN cells (CD2+ CD7+ and CD2- CD7-) indicate that infected TN cells may correspond to both immature thymocytes and thymic dendritic cells. These data are of particular interest since infection of thymic stromal cells might result in an impairment of T-cell differentiation, which may explain a nongeneration of functional CD4+ T-cell population in the thymus. This phenomenon may play a role in AIDS pathogenesis, in particular in infants born from seropositive mothers.
一些感染了1型人类免疫缺陷病毒（HIV-1）的婴儿会迅速患上一种以严重淋巴细胞减少为特征的致命疾病。为了解释这种免疫功能障碍，我们提出了一种机制，即HIV-1感染胸腺细胞导致CD4+ T细胞无法生成。为了验证这一假设，我们感染了原代三阴性（TN；表型为CD3- CD4- CD8-）、CD1a- TN或CD1a+ TN胸腺细胞亚群。我们的数据表明，通过流式细胞术检测，TN、CD1a- TN和CD1a+ TN细胞在整个培养期内均保持CD4阴性。我们证明，TN和CD1a+ TN胸腺细胞亚群与整个胸腺细胞群体一样，对HIV-1敏感，而CD1a- TN细胞则不敏感。通过原位杂交检测发现，有限数量的受感染TN细胞表达HIV-1，但在允许性细胞中转录水平非常高。然后，我们对TN细胞进行了阻断实验，以研究HIV-1进入这些细胞的机制。CD4（OKT4a）单克隆抗体可阻断它们的感染。最后，对TN细胞的两个亚群（CD2+ CD7+和CD2- CD7-）进行的感染实验表明，受感染的TN细胞可能既包括未成熟胸腺细胞，也包括胸腺树突状细胞。这些数据特别令人关注，因为胸腺基质细胞的感染可能导致T细胞分化受损，这可能解释了胸腺中功能性CD4+ T细胞群体无法生成的原因。这种现象可能在艾滋病发病机制中起作用，尤其是在血清反应阳性母亲所生的婴儿中。
