法国巴黎大学Jean-Laurent Casanova和Vivien Béziat课题组合作发现，遗传性T细胞CD28缺陷的人容易感染皮肤乳头瘤病毒，但在其他方面是健康的。该研究于2021年7月1日发表于国际一流学术期刊《细胞》杂志上。
他们研究了一名患有人类乳头瘤病毒 (HPV)-2 驱动的“树人”表型的患者和两个患有异常严重的 HPV4 驱动疣的亲属。巨角形成 HPV-2 驱动的多灶性良性上皮肿瘤，在表皮基底层过度表达病毒癌基因。这些患者出乎意料地是私密CD28 变体的纯合子。除了一小部分回复性记忆 CD4+ T 细胞外，它们的 T 细胞上没有可检测到的 CD28。 T 细胞发育几乎不受影响，T 细胞对 CD3 和 CD2 有反应，但对 CD28 共刺激没有反应。
尽管这些患者在体外没有表现出 HPV-2 和 HPV-4 反应性 CD4+ T 细胞，但他们在体内产生了针对这两种病毒的特异性抗体。CD28 缺陷小鼠容易受到小鼠乳头瘤病毒 MmuPV1 的皮肤感染。角质形成细胞中 HPV-2 和 HPV-4 的控制依赖于 T 细胞 CD28 共激活途径。令人惊讶的是，人类 CD28 依赖性 T 细胞反应对于保护性免疫而言在很大程度上是多余的。
附：英文原文
Title: Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy
Author: Vivien Béziat, Franck Rapaport, Jiafen Hu, Matthias Titeux, Mathilde Bonnet des Claustres, Mathieu Bourgey, Heather Griffin, élise Bandet, Cindy S. Ma, Roya Sherkat, Hassan Rokni-Zadeh, David M. Louis, Majid Changi-Ashtiani, Ottavia M. Delmonte, Toshiaki Fukushima, Tanwir Habib, Andrea Guennoun, Taushif Khan, Noemi Bender, Mahbuba Rahman, Frédégonde About, Rui Yang, Geetha Rao, Claire Rouzaud, Jingwei Li, Debra Shearer, Karla Balogh, Fatima Al Ali, Manar Ata, Soroosh Dabiri, Mana Momenilandi, Justine Nammour, Marie-Alexandra Alyanakian, Marianne Leruez-Ville, David Guenat, Marie Materna, Léa Marcot, Natasha Vladikine, Christine Soret, Hassan Vahidnezhad, Leila Youssefian, Amir Hossein Saeidian, Jouni Uitto, émilie Catherinot, Shadi Sadat Navabi, Mohammed Zarhrate, David T. Woodley, Mohamed Jeljeli, Thomas Abraham, Serkan Belkaya, Lazaro Lorenzo, Jérémie Rosain, Mousa Bayat, Fanny Lanternier, Olivier Lortholary, Faramarz Zakavi, Philippe Gros, Gérard Orth, Laurent Abel, Jean-Luc Prétet, Sylvie Fraitag, Emmanuelle Jouanguy, Mark M. Davis, Stuart G. Tangye, Luigi D. Notarangelo, Nico Marr, Tim Waterboer, David Langlais, John Doorbar
Issue&Volume: 2021-07-01
Abstract: We study a patient with the human papilloma virus (HPV)-2-driven “tree-man” phenotypeand two relatives with unusually severe HPV4-driven warts. The giant horns form anHPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes inthe epidermis basal layer. The patients are unexpectedly homozygous for a privateCD28 variant. They have no detectable CD28 on their T cells, with the exception of a smallcontingent of revertant memory CD4+ T cells. T cell development is barely affected, and T cells respond to CD3 and CD2,but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactiveCD4+ T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirusMmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cellCD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses arelargely redundant for protective immunity.
DOI: 10.1016/j.cell.2021.06.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00705-4