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

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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Work Title Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy
Access
Open Access
Creators
  1. Vivian Beziat
  2. Franck Rapaport
  3. Jiafen Hu
  4. Matthias Titeux
  5. Mathilde Bonnet des Claustres
  6. Mathieu Bourgey
  7. Heather Griffin
  8. Elise Bandet
  9. Cindy S. Ma
  10. Roya Sherkat
  11. Hassan Rokni-Zadeh
  12. David M. Louis
  13. Majid Changi-Ashtiani
  14. Ottavia M. Delmonte
  15. Toshiaki Fukushima
  16. Tanwir Habib
  17. Andrea Guennoun
  18. Taushif Khan
  19. Noemi Bender
  20. Mahbuba Rahman
  21. Frédégonde About
  22. Rui Yang
  23. Geetha Rao
  24. Claire Rouzaud
  25. Jingwei Li
  26. Debra Shearer
  27. Karla Balogh
  28. Fatima Al Ali
  29. Manar Ata
  30. Soroosh Dabiri
  31. Mana Momenilandi
  32. Justine Nammour
  33. Marie-Alexandra Alyanakian
  34. Marianne Leruez-Ville
  35. David Guenat
  36. Marie Materna
  37. Léa Marcot
  38. Natasha Vladikine
  39. Christine Soret
  40. Hassan Vahidnezhad
  41. Leila Youssefian
  42. Amir Hossein Saeidian
  43. Jouni Uitto
  44. Émilie Catherinot
  45. Shadi Sadat Navabi
  46. Mohammed Zarhrate
  47. David T. Woodley
  48. Mohamed Jeljeli
  49. Thomas Abraham
  50. Serkan Belkaya
  51. Lazaro Lorenzo
  52. Jérémie Rosain
  53. Mousa Bayat
  54. Fanny Lanternier
  55. Olivier Lortholary
  56. Faramarz Zakavi
  57. Philippe Gros
  58. Gérard Orth
  59. Laurent Abel
  60. Jean-Luc Prétet
  61. Sylvie Fraitag
  62. Emmanuelle Jouanguy
  63. Mark M. Davis
  64. Stuart G. Tangye
  65. Luigi D. Notarangelo
  66. Nico Marr
  67. Tim Waterboer
  68. David Langlais
  69. John Doorbar
  70. Alain Hovnanian
  71. Neil Christensen
  72. Xavier Bossuyt
  73. Mohammad Shahrooei
  74. Jean-Laurent Casanova
Keyword
  1. CD28
  2. T cell
  3. Papillomavirus
  4. HPV
  5. Wart
  6. Tree Man Syndrome
  7. Cutaneous horn
  8. Oncogene
  9. Somatic reversion
  10. Immunodeficiency
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Cell
Publication Date July 8, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1016/j.cell.2021.06.004
Deposited January 30, 2023

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Version 1
published

  • Created
  • Added cell_2021_1-s2.0-S0092867421007054-main.pdf
  • Added Creator Jiafen Hu
  • Published
  • Updated Work Title, Keyword, Publisher, and 2 more Show Changes
    Work Title
    • Inherited CD28 deficiency in otherwise healthy patients with disseminated warts and giant horns
    • Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy
    Keyword
    • CD28, T cell, Papillomavirus, HPV, Wart, Tree Man Syndrome, Cutaneous horn, Oncogene, Somatic reversion, Immunodeficiency
    Publisher
    • cell
    • Cell
    Publisher Identifier (DOI)
    • https://doi.org/10.1016/j.cell.2021.06.004
    Description
    • 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.
    • 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.
  • Updated Creator Jiafen Hu
  • Added Creator Vivian Beziat
  • Added Creator Franck Rapaport
  • Added Creator Matthias Titeux
  • Added Creator Mathilde Bonnet des Claustres
  • Added Creator Mathieu Bourgey
  • Added Creator Heather Griffin
  • Added Creator Elise Bandet
  • Added Creator Cindy S. Ma
  • Added Creator Roya Sherkat
  • Added Creator Hassan Rokni-Zadeh
  • Added Creator David M. Louis
  • Added Creator Majid Changi-Ashtiani
  • Added Creator Ottavia M. Delmonte
  • Added Creator Toshiaki Fukushima
  • Added Creator Tanwir Habib
  • Added Creator Andrea Guennoun
  • Added Creator Taushif Khan
  • Added Creator Noemi Bender
  • Added Creator Mahbuba Rahman
  • Added Creator Frédégonde About
  • Added Creator Rui Yang
  • Added Creator Geetha Rao
  • Added Creator Claire Rouzaud
  • Added Creator Jingwei Li
  • Added Creator Debra Shearer
  • Added Creator 3 31, Karla Balogh
  • Added Creator Fatima Al Ali
  • Added Creator Manar Ata
  • Added Creator Soroosh Dabiri
  • Added Creator Mana Momenilandi
  • Added Creator Justine Nammour
  • Added Creator Marie-Alexandra Alyanakian
  • Added Creator Marianne Leruez-Ville
  • Added Creator David Guenat
  • Added Creator Marie Materna
  • Added Creator Léa Marcot
  • Added Creator Natasha Vladikine
  • Added Creator Christine Soret
  • Added Creator Hassan Vahidnezhad
  • Added Creator Leila Youssefian
  • Added Creator Amir Hossein Saeidian
  • Added Creator Jouni Uitto
  • Added Creator Émilie Catherinot
  • Added Creator Shadi Sadat Navabi
  • Added Creator Mohammed Zarhrate
  • Added Creator David T. Woodley
  • Added Creator Mohamed Jeljeli
  • Added Creator Thomas Abraham
  • Added Creator Serkan Belkaya
  • Added Creator Lazaro Lorenzo
  • Added Creator Jérémie Rosain
  • Added Creator Mousa Bayat
  • Added Creator Fanny Lanternier
  • Added Creator Olivier Lortholary
  • Added Creator Faramarz Zakavi
  • Added Creator Philippe Gros
  • Added Creator Gérard Orth
  • Added Creator Laurent Abel
  • Added Creator Jean-Luc Prétet
  • Added Creator Sylvie Fraitag
  • Added Creator Emmanuelle Jouanguy
  • Added Creator Mark M. Davis
  • Added Creator Stuart G. Tangye
  • Added Creator Luigi D. Notarangelo
  • Added Creator Nico Marr
  • Added Creator Tim Waterboer
  • Added Creator David Langlais
  • Added Creator John Doorbar
  • Added Creator Alain Hovnanian
  • Added Creator Neil Christensen
  • Added Creator Xavier Bossuyt
  • Added Creator Mohammad Shahrooei
  • Added Creator Jean-Laurent Casanova
  • Renamed Creator Karla Balogh Show Changes
    • 3 31, Karla Balogh
    • Karla Balogh
  • Updated