학술논문

Helper T cell immunity in humans with inherited CD4 deficiency.
Document Type
Academic Journal
Author
Guérin A; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.; Moncada-Vélez M; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.; Jackson K; Garvan Institute of Medical Research , Darlinghurst, Australia.; Ogishi M; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Rosain J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris , Paris, France.; Mancini M; Department of Human Genetics, McGill University, Montreal, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, Canada.; Dahdaleh Institute of Genomic Medicine, McGill Research Centre on Complex Traits, McGill University , Montreal, Canada.; Langlais D; Department of Human Genetics, McGill University, Montreal, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, Canada.; Dahdaleh Institute of Genomic Medicine, McGill Research Centre on Complex Traits, McGill University , Montreal, Canada.; Nunez A; Department of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.; Webster S; Department of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.; Goyette J; Department of Molecular Medicine, School of Biomedical Sciences, University of New South Wales, Sydney, Australia.; Khan T; Department of Human Immunology, Sidra Medicine, Doha, Qatar.; The Jackson Laboratory , Farmington, CT, USA.; Marr N; Department of Human Immunology, Sidra Medicine, Doha, Qatar.; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.; Avery DT; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.; Rao G; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.; Waterboer T; Division of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.; Michels B; Division of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.; Neves E; Immunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.; Iracema Morais C; Immunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.; London J; Service of Internal Medicine, Diaconesse-Croix Saint Simon Hospital , Paris, France.; Mestrallet S; Department of Internal Medicine and Infectious Diseases, Manchester Hospital, Charleville-Mézières, France.; Quartier Dit Maire P; Pediatric Immunology-Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Paris, France.; Neven B; Pediatric Immunology-Hematology and Rheumatology Unit, Necker Hospital for Sick Children, Paris, France.; Rapaport F; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Seeleuthner Y; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Lev A; Department of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.; Simon AJ; Department of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.; Montoya J; San Vicente de Paul University Hospital , Medellin, Colombia.; Barel O; The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.; Gómez-Rodríguez J; National Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.; Orrego JC; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.; L'Honneur AS; Department of Virology, Paris Cité University and Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Soudée C; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Rojas J; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.; Velez AC; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.; Sereti I; National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.; Terrier B; Department of Internal Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, Paris, France.; Marin N; Cellular Immunology and Immunogenetics Group, University of Antioquia UdeA , Medellin, Colombia.; García LF; Cellular Immunology and Immunogenetics Group, University of Antioquia UdeA , Medellin, Colombia.; Abel L; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Boisson-Dupuis S; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Reis J; Dermatology Service, University Hospital Center of Porto, Porto, Portugal.; Marinho A; School of Medicine and Biomedical Sciences, University of Porto , Porto, Portugal.; Department of Clinical Immunology, University Hospital Center of Porto, Porto, Portugal.; Lisco A; National Human Genome Research Institute, National Institutes of Health , Bethesda, MD, USA.; Faria E; Allergy and Clinical Immunology Department, University Hospital Center of Coimbra, Coimbra, Portugal.; Goodnow CC; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.; Vasconcelos J; Immunology Department-Pathology, University Hospital Center of Porto, Porto, Portugal.; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.; Béziat V; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Ma CS; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.; Somech R; Department of Pediatrics and Immunology Service , Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv School of Medicine, Tel Aviv, Israel.; Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Howard Hughes Medical Institute , New York, NY, USA.; Department of Pediatrics, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.; Bustamante J; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris , Paris, France.; Franco JL; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia UdeA, Medellin, Colombia.; Tangye SG; Garvan Institute of Medical Research , Darlinghurst, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, University of New South Wales Sydney, Sydney, Australia.
Source
Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
Subject
Language
English
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.
(© 2024 Guérin et al.)