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

Fiche publication

Date publication

juin 2021

Journal

Cell

Auteurs

Membres identifiés du Cancéropôle Est :
Pr PRETET Jean-Luc

Tous les auteurs :
Béziat V, Rapaport F, Hu J, Titeux M, Bonnet des Claustres M, Bourgey M, Griffin H, Bandet É, Ma CS, Sherkat R, Rokni-Zadeh H, Louis DM, Changi-Ashtiani M, Delmonte OM, 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 MA, Leruez-Ville M, Guenat D, Materna M, Marcot L, Vladikine N, Soret C, Vahidnezhad H, Youssefian L, Saeidian AH, Uitto J, Catherinot É, Navabi SS, Zarhrate M, Woodley DT, Jeljeli M, Abraham T, Belkaya S, Lorenzo L, Rosain J, Bayat M, Lanternier F, Lortholary O, Zakavi F, Gros P, Orth G, Abel L, Prétet JL, Fraitag S, Jouanguy E, Davis MM, Tangye SG, Notarangelo LD, Marr N, Waterboer T, Langlais D, Doorbar J, Hovnanian A, Christensen N, Bossuyt X, Shahrooei M, Casanova JL

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34214472

Résumé

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.