期刊
CELL
卷 184, 期 14, 页码 3812-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.06.004
关键词
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资金
- regional Tumor Bank of Franche-Comte (TRFC) [BB-0033-00024]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID, ANR-11-LABX-0021]
- French National Agency for Research [ANR-10-IAHU-01, NKIR-ANR-13-PDOC-0025-01]
- National Institutes of Health Clinical and Translational Science Award program
- Research Fund of Pathology Department and Cancer Institute of Penn State University College of Medicine
- JSPS KAKENHI [19H05289]
- Qatar National Research Fund [NPRP9-251-3-045]
- Grants-in-Aid for Scientific Research [19H05289] Funding Source: KAKEN
The study investigated a patient with HPV-2-driven "tree-man" phenotype and two relatives with severe HPV4-driven warts, revealing the relationship between a CD28 variant and T cell responses. Findings suggest that T cell responses are important in controlling HPV infections.
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.
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