ArticleThe Journal of experimental medicine2024
Helper T cell immunity in humans with inherited CD4 deficiency.
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Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Human CD21Journal of human immunity · 2026Review
- IRF4 haploinsufficiency in a multiplex family with Whipple's disease.Journal of human immunity · 2026Article
- Human genetics of Whipple's disease.Current opinion in rheumatology · 2025Review
- Cutaneous Innate Lymphoid Populations Drive IL-17A-Mediated Immunity in Nannizzia gypsea Dermatophytosis.The Journal of investigative dermatology · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- CD4 expression controls epidermal stem cell balance.Scientific reports · 2025Article
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
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Authors and funding
53 authors at 19 institutions in 9 countries.
Antoine GuérinGarvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0001-6810-1607
Marcela Moncada-Vélez *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-3073-5345
Katherine Jackson *Garvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0002-9952-7069
Masato Ogishi *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0003-2421-7389
Jérémie RosainSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-2822-161X
Mathieu ManciniDepartment of Human Genetics, McGill University, Montreal, Canada.ORCID 0000-0002-4981-7121
David LanglaisDepartment of Human Genetics, McGill University, Montreal, Canada.ORCID 0000-0003-4429-0110
Andrea NunezDepartment of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.ORCID 0000-0002-0182-1834
Samantha WebsterDepartment of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.ORCID 0000-0003-2494-5191
Jesse GoyetteDepartment of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.ORCID 0000-0002-1008-1890
Taushif KhanDepartment of Human Immunology, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-7917-8965
Nico MarrDepartment of Human Immunology, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-1927-7072
Danielle T AveryGarvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0002-9156-0489
Geetha RaoGarvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0009-0007-2744-9309
Tim WaterboerDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.ORCID 0000-0002-0616-6963
Birgitta MichelsDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.ORCID 0000-0001-9948-4567
Esmeralda NevesImmunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.ORCID 0000-0002-7754-8109
Cátia Iracema MoraisImmunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.ORCID 0000-0003-2814-9248
Jonathan LondonService of Internal Medicine, Diaconesse-Croix Saint Simon Hospital , Paris, France.ORCID 0000-0002-8857-111X
Stéphanie MestralletDepartment of Internal Medicine and Infectious Diseases, Manchester Hospital, Charleville-Mézières, France.ORCID 0009-0007-6427-6128
Pierre Quartier Dit MairePediatric Immunology-Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-1769-549X
Bénédicte NevenPediatric Immunology-Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0001-8941-0935
Franck RapaportSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0001-6553-2110
Yoann SeeleuthnerLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.ORCID 0009-0000-2670-6026
Atar LevDepartment of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.ORCID 0000-0003-3416-1243
Amos J SimonDepartment of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.ORCID 0000-0003-0511-4122
Jorge MontoyaSan Vicente de Paul University Hospital , Medellin, Colombia.ORCID 0000-0002-6983-4770
Ortal BarelThe Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.ORCID 0000-0003-1168-9758
Julio Gómez-RodríguezNational Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0007-9708-419X
Julio C OrregoPrimary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.ORCID 0000-0002-3809-9187
Anne-Sophie L'HonneurDepartment of Virology, Paris Cité University and Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID 0000-0002-9228-0649
Camille SoudéeLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.ORCID 0009-0002-1445-7223
Jessica RojasPrimary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.ORCID 0000-0002-5578-8160
Alejandra C VelezPrimary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.ORCID 0000-0001-9157-8390
Irini SeretiNational Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-0076-0224
Benjamin TerrierDepartment of Internal Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, Paris, France.ORCID 0000-0001-6612-7336
Nancy MarinCellular Immunology and Immunogenetics Group, University of Antioquia UdeA , Medellin, Colombia.ORCID 0000-0002-2626-3349
Luis F GarcíaCellular Immunology and Immunogenetics Group, University of Antioquia UdeA , Medellin, Colombia.ORCID 0000-0002-5343-0050
Laurent AbelSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0001-7016-6493
Stéphanie Boisson-DupuisSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-7115-116X
Joel ReisDermatology Service, University Hospital Center of Porto, Porto, Portugal.ORCID 0000-0002-8007-2420
Antonio MarinhoSchool of Medicine and Biomedical Sciences, University of Porto , Porto, Portugal.
Andrea LiscoNational Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-1475-356X
Emilia FariaAllergy and Clinical Immunology Department, University Hospital Center of Coimbra, Coimbra, Portugal.ORCID 0000-0002-9602-1599
Christopher C GoodnowGarvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0001-5296-6155
Julia VasconcelosImmunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.ORCID 0000-0002-7315-5703
Vivien Béziat *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-4020-824X
Cindy S Ma *Garvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0001-5387-8413
Raz Somech *Department of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.ORCID 0000-0001-6648-9425
Jean-Laurent Casanova *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-7782-4169
Jacinta Bustamante *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-3439-2482
Jose Luis Franco *Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.ORCID 0000-0001-5664-6415
Stuart G Tangye *Garvan Institute of Medical Research , Darlinghurst, Australia.ORCID 0000-0002-5360-5180
Garvan Institute of Medical Research · AUInserm · FRUniversidad de Antioquia · COUniversidade do Porto · PTHôpital Necker-Enfants Malades · FRNational Institutes of Health · USTel Aviv University · ILUNSW Sydney · AUGerman Cancer Research Center · DEMcGill Genome Centre · CAQatar Airways (Qatar) · QARockefeller University · USUniversité Paris Cité · FRCUF Porto Hospital · PTGroupe Hospitalier Diaconesses Croix Saint-Simon · FRHôpital Manchester · FRHospital Universitario de San Vicente Fundación · COSheba Medical Center · ILUniversity of Coimbra · PT
Funding
Immunopathogenic Mechanisms of Human Immunodeficiency Virus (HIV) DiseaseZIAAI001121 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SERETI, IRINI · 2010 to 2025
$27.2MImmunopathogenesis of skin and mucosal Human Papillomavirus (HPV)-related diseases ZIAAI001310 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LISCO, ANDREA · 2020 to 2025
$2.7MGenome-Wide Dissection of Mendelian Susceptibility to Mycobacterial DiseaseR01AI095983 · NIAID · ROCKEFELLER UNIVERSITY · PI BUSTAMANTE, JACINTA, CASANOVA, JEAN-LAURENT · 2021 to 2025
$2.5MAmerican Association of ImmunologistsBettencourt-Schueller FoundationDavid Rockefeller Graduate ProgramECOS-Nord/Ministerio de Ciencia, Tecnología e Innovación of Colombia CT 806-2018/046-2019French National Research Agency ANR-10-IAHU-01Funai Foundation for Information TechnologyGENMSMD ANR-16-CE17.0005-01Honjo International Scholarship FoundationImagine InstituteINCaInstitut National de la Santé et de la Recherche MédicaleITMO Cancer of AviesanLaboratoire d'Excellence Integrative-Biology of Emerging Infectious Diseases ANR-10-LABX-62-IBEILatin American Society for Primary ImmunodeficienciesNational Health and Medical Research Council 1176665, 2017463National Institute of Allergy and Infectious Diseases R01AI095983New York Hideyo Noguchi Memorial SocietyNIAID NIH HHS R01 AI095983Paris Cité UniversityRockefeller UniversityScheinberg FellowshipSt. Giles Foundation
Abstract
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.
Indexed as
CD4-Positive T-LymphocytesT-Lymphocytes, Helper-InducerCD8-Positive T-LymphocytesHLA AntigensHumansLymphocyte ActivationProtein IsoformsHLA AntigensProtein Isoforms
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