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

First Author  Béziat V Year  2021
Journal  Cell Volume  184
Issue  14 Pages  3812-3828.e30
PubMed ID  34214472 Mgi Jnum  J:313727
Mgi Id  MGI:6728437 Doi  10.1016/j.cell.2021.06.004
Citation  Beziat V, et al. (2021) Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy. Cell 184(14):3812-3828.e30
abstractText  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.
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