Helper T cell immunity in humans with inherited CD4 deficiency

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.

• Autores: Moncada Vélez, Marcela; Franco Restrepo, José Luis; Vélez Ortega, Alejandra Catalina; Rojas Restrepo, Jessica Lineth; Orrego Arango, Julio César; García Moreno, Luis Fernando; Marín Agudelo, Nancy Dora; Guérin, Antoine; Jackson, Katherine; Ogishi, Masato; Rosain, Jérémie; Mancini, Mathieu; Nunez, Andrea; Webster, Samantha; Goyette, Jesse; Khan, Taushif; Marr, Nico; Avery, Danielle T.; Rao, Geetha; Waterboer, Tim; Michels, Birgitta; Neves, Esmeralda; Morais, Cátia Iracema; London, Jonathan; Quartier dit Maire, Pierre; Mestrallet, Stéphanie; Neven, Bénédicte; Rapaport, Franck; Seeleuthner, Yoann; Lev, Atar; Simon, Amos J.; Montoya, Jorge; Barel, Ortal; L’Honneur, Anne Sophie; Soudée, Camille; Sereti, Irini; Terrier, Benjamin; 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; Tangye, Stuart G.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2024
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/43137
• Acceso en línea: https://hdl.handle.net/10495/43137
• Palabra clave: Linfocitos T CD4-Positivos; CD4-Positive T-Lymphocytes; Linfocitos T CD8-positivos; CD8-Positive T-Lymphocytes; Antígenos HLA; HLA Antigens; Activación de Linfocitos; Lymphocyte Activation; Isoformas de Proteínas - metabolismo; Protein Isoforms - metabolism; Linfocitos T Colaboradores-Inductores; T-Lymphocytes, Helper-Inducer; https://id.nlm.nih.gov/mesh/D015496; https://id.nlm.nih.gov/mesh/D018414; https://id.nlm.nih.gov/mesh/D006680; https://id.nlm.nih.gov/mesh/D008213; https://id.nlm.nih.gov/mesh/D020033; https://id.nlm.nih.gov/mesh/D006377
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/