Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy

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 RahmanFrédégonde 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, Alain Hovnanian, Neil Christensen, Xavier Bossuyt, Mohammad Shahrooei, Jean Laurent Casanova

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


We study a patient with the human papilloma virus (HPV)-2-driven “tree-man” phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent 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-reactive CD4+ T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity.

Original languageEnglish (US)
Pages (from-to)3812-3828.e30
Issue number14
StatePublished - Jul 8 2021

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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