| Title: |
Helper T cell immunity in humans with inherited CD4 deficiency |
| Authors: |
Guérin, Antoine; Moncada-Vélez, Marcela; Jackson, Katherine; Ogishi, Masato; Rosain, Jérémie; Mancini, Mathieu; Langlais, David; Nunez, Andrea; Webster, Samantha; Goyette, Jesse; Khan, Taushif; Marr, Nico; Avery, Danielle, T; Rao, Geetha; Waterboer, Tim; Michels, Birgitta; Neves, Esmeralda; Iracema Morais, Cátia; London, Jonathan; Mestrallet, Stéphanie; Quartier Dit Maire, Pierre; Neven, Bénédicte; Rapaport, Franck; Seeleuthner, Yoann; Lev, Atar; Simon, Amos, J; Montoya, Jorge; Barel, Ortal; Gómez-Rodríguez, Julio; Orrego, Julio, C; L’honneur, Anne-Sophie; Soudée, Camille; Rojas, Jessica; Velez, Alejandra, C; Sereti, Irini; Terrier, Benjamin; Marin, Nancy; García, Luis, F; Abel, Laurent; Boisson-Dupuis, Stéphanie; Reis, Joel; Marinho, Antonio; Lisco, Andrea; Faria, Emilia; Goodnow, Christopher, C; Vasconcelos, Julia; Béziat, Vivien; Ma, Cindy, S; Somech, Raz; Casanova, Jean-Laurent; Bustamante, Jacinta; Franco, Jose Luis; Tangye, Stuart, G |
| Contributors: |
University of Sydney, Sydney NSW 2006 Australia; Rockefeller University New York; Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); McGill University = Université McGill Montréal, Canada; Department of Physiology and EMBL Australia Node for Single Molecule Science; Sidra Medicine Doha, Qatar; Hamad Bin Khalifa University Doha, Qatar (HBKU); Garvan Institute of medical research; German Cancer Research Center - Deutsches Krebsforschungszentrum Heidelberg (DKFZ); Unidade de Imunologia Clínica, Centro Hospitalar do Porto, Portugal; Centre Hospitalier de Charleville-Mezières; Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Université Paris Cité (UPCité); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); AP-HP - Hôpital Cochin Broca Hôtel Dieu Paris; National Institute of Allergy and Infectious Diseases Bethesda (NIAID-NIH); National Institutes of Health Bethesda, MD, USA (NIH); Hôpital Cochin AP-HP; Universidad de Antioquia = University of Antioquia Medellín, Colombia; ITMO Cancer ofAviesan and INCa within the framework of the 2021–2030Cancer Control Strategy (on funds administered by INSERM); ECOS-Nord/Ministerio deCiencia, Tecnolog´ıa e Innovación of Colombia (CT 806-2018/046-2019; ANR-21-CE15-0034,CARMIL2,Bases moléculaires, cellulaires et immunologiques de la déficience combinée résultant de mutations dans CARMIL2(2021); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010); ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016) |
| Source: |
ISSN: 0022-1007. |
| Publisher Information: |
CCSD; Rockefeller University Press |
| Publication Year: |
2024 |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5–61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple’s disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4−CD8− T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4−CD8− αβ T cells exhibit intact responses to HLA class II–restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1084/jem.20231044 |
| Availability: |
https://hal.science/hal-04916491; https://hal.science/hal-04916491v1/document; https://hal.science/hal-04916491v1/file/jem_20231044.pdf; https://doi.org/10.1084/jem.20231044 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.47998560 |
| Database: |
BASE |