Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy.
Cell
; 184(14): 3812-3828.e30, 2021 07 08.
Article
in En
| MEDLINE
| ID: mdl-34214472
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Papillomaviridae
/
Skin
/
T-Lymphocytes
/
CD28 Antigens
/
Inheritance Patterns
Limits:
Adult
/
Animals
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cell
Year:
2021
Type:
Article