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

被引：70

作者：

Beziat, Vivien ^{[1
,2
]}

Rapaport, Franck ^{[2
]}

Hu, Jiafen ^{[3
]}

Titeux, Matthias ^{[1
]}

des Claustres, Mathilde Bonnet ^{[1
]}

Bourgey, Mathieu ^{[4
]}

Griffin, Heather ^{[5
]}

Bandet, Elise ^{[1
]}

Ma, Cindy S. ^{[6
,7
]}

Sherkat, Roya ^{[8
]}

Rokni-Zadeh, Hassan ^{[9
]}

Louis, David M. ^{[10
]}

Changi-Ashtiani, Majid ^{[11
]}

Delmonte, Ottavia M. ^{[12
]}

Fukushima, Toshiaki ^{[13
]}

Habib, Tanwir ^{[14
]}

Guennoun, Andrea ^{[14
]}

Khan, Taushif ^{[14
]}

Bender, Noemi ^{[12
]}

Rahman, Mahbuba ^{[13
]}

About, Fredegonde ^{[1
]}

Yang, Rui ^{[2
]}

Rao, Geetha ^{[6
,7
]}

Rouzaud, Claire ^{[1
,16
]}

Li, Jingwei ^{[3
]}

Shearer, Debra ^{[3
]}

Balogh, Karla ^{[3
]}

Al Ali, Fatima ^{[14
]}

Ata, Manar ^{[14
]}

Dabiri, Soroosh ^{[17
]}

Momenilandi, Mana ^{[18
]}

Nammour, Justine ^{[1
]}

Alyanakian, Marie-Alexandra ^{[16
]}

Leruez-Ville, Marianne ^{[16
]}

Guenat, David ^{[19
]}

Materna, Marie ^{[1
]}

Marcot, Lea ^{[1
]}

Vladikine, Natasha ^{[1
]}

Soret, Christine ^{[19
]}

Vahidnezhad, Hassan ^{[20
]}

Youssefian, Leila ^{[20
]}

Saeidian, Amir Hossein ^{[20
]}

Uitto, Jouni ^{[20
]}

Catherinot, Emilie ^{[21
]}

Navabi, Shadi Sadat ^{[22
]}

Zarhrate, Mohammed ^{[1
]}

Woodley, David T. ^{[23
]}

Jeljeli, Mohamed ^{[24
]}

Abraham, Thomas ^{[3
]}

Belkaya, Serkan ^{[2
]}

机构：

[1] Univ Paris, Imagine Inst, INSERM, U1163, F-75015 Paris, France

[2] Rockefeller Univ, New York, NY 10065 USA

[3] Penn State Univ, Coll Med, Hershey, PA 17033 USA

[4] McGill Univ, Montreal, PQ H3A 0G1, Canada

[5] Univ Cambridge, Cambridge CB2 1QP, England

[6] Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia

[7] UNSW Sydney, St Vincents Clin Sch, Sydney, NSW 2052, Australia

[8] Isfahan Univ Med Sci, AIRC, Esfahan 8174673461, Iran

[9] Zanjan Univ Med Sci, Zanjan 4513956184, Iran

[10] Stanford Univ, Med Sch, Stanford, CA 94305 USA

[11] Inst Res Fundamental Sci IPM, Tehran 193955746, Iran

[12] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[13] Tokyo Inst Technol, Inst Innovat Res, Yokohama, Kanagawa 2268501, Japan

[14] Sidra Med, Doha, Qatar

[15] German Canc Res Ctr, D-69120 Heidelberg, Germany

[16] Necker Hosp Sick Children, AP HP, F-75015 Paris, France

[17] Zahedan Univ Med Sci, Zahedan 054, Iran

[18] Univ Leuven, B-3000 Leuven, Belgium

[19] Besancon Hosp, Papillomavirus Natl Reference Ctr, F-25030 Besancon, France

[20] Thomas Jefferson Univ, Philadelphia, PA 19107 USA

[21] Foch Hosp, F-92150 Suresnes, France

[22] Dr Shahrooei Lab, Ahvaz, Iran

[23] Univ Southern Calif, Los Angeles, CA 90033 USA

[24] Cochin Univ Hosp, AP HP, F-75014 Paris, France

[25] Ahvaz Jundishapur Univ Med Sci, Ahvaz 061, Iran

[26] McGill Res Ctr Complex Traits, Montreal, PQ H3G 0B1, Canada

[27] Pasteur Inst, F-75015 Paris, France

[28] Stanford Univ, Med Sch, HHMI, Stanford, CA 94305 USA

[29] HHMI, New York, NY 10065 USA

来源：

CELL | 2021年 / 184卷 / 14期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

GLUTATHIONE-S-TRANSFERASE; CYTOMEGALOVIRUS-INFECTION; MOLECULAR-BIOLOGY; SOMATIC MUTATION; EXPRESSION; COSTIMULATION; INTEGRATION; HPV; SPECIFICITY; PROGRESSION;

D O I：

10.1016/j.cell.2021.06.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3812 / +

页数：47

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