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Repository of Research and Investigative Information

Zahedan University of Medical Sciences

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

(2021) Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy. Cell. 3812-+. ISSN 0092-8674

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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 themouse 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.

Item Type: Article
Keywords: glutathione-s-transferase cytomegalovirus-infection molecular-biology somatic mutation expression costimulation integration population hpv DNA Biochemistry & Molecular Biology Cell Biology
Page Range: 3812-+
Journal or Publication Title: Cell
Journal Index: ISI
Volume: 184
Number: 14
Identification Number: https://doi.org/10.1016/j.cell.2021.06.004
ISSN: 0092-8674
Depositing User: مهندس مهدی شریفی
URI: http://eprints.zaums.ac.ir/id/eprint/5418

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