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


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.

Type Journal
ISBN 1097-4172 (Electronic) 0092-8674 (Linking)
Authors Beziat, V.; Rapaport, F.; Hu, J.; Titeux, M.; Bonnet des Claustres, M.; Bourgey, M.; Griffin, H.; Bandet, E.; Ma, C. S.; Sherkat, R.; Rokni-Zadeh, H.; Louis, D. M.; Changi-Ashtiani, M.; Delmonte, O. M.; Fukushima, T.; Habib, T.; Guennoun, A.; Khan, T.; Bender, N.; Rahman, M.; About, F.; Yang, R.; Rao, G.; Rouzaud, C.; Li, J.; Shearer, D.; Balogh, K.; Al Ali, F.; Ata, M.; Dabiri, S.; Momenilandi, M.; Nammour, J.; Alyanakian, M. A.; Leruez-Ville, M.; Guenat, D.; Materna, M.; Marcot, L.; Vladikine, N.; Soret, C.; Vahidnezhad, H.; Youssefian, L.; Saeidian, A. H.; Uitto, J.; Catherinot, E.; Navabi, S. S.; Zarhrate, M.; Woodley, D. T.; Jeljeli, M.; Abraham, T.; Belkaya, S.; Lorenzo, L.; Rosain, J.; Bayat, M.; Lanternier, F.; Lortholary, O.; Zakavi, F.; Gros, P.; Orth, G.; Abel, L.; Pretet, J. L.; Fraitag, S.; Jouanguy, E.; Davis, M. M.; Tangye, S. G.; Notarangelo, L. D.; Marr, N.; Waterboer, T.; Langlais, D.; Doorbar, J.; Hovnanian, A.; Christensen, N.; Bossuyt, X.; Shahrooei, M.; Casanova, J. L.
Responsible Garvan Author A/Prof Cindy Ma
Publisher Name CELL
Published Date 2021-07-31
Published Volume 184
Published Issue 14
Published Pages 3812-3828 e30
Status Published in-print
DOI 10.1016/j.cell.2021.06.004
URL link to publisher's version