TY  - JOUR
AU  - Guérin, Antoine
AU  - Moncada-Vélez, Marcela
AU  - Jackson, Katherine
AU  - Ogishi, Masato
AU  - Rosain, Jérémie
AU  - Mancini, Mathieu
AU  - Langlais, David
AU  - Nunez, Andrea
AU  - Webster, Samantha
AU  - Goyette, Jesse
AU  - Khan, Taushif
AU  - Marr, Nico
AU  - Avery, Danielle T
AU  - Rao, Geetha
AU  - Waterboer, Tim
AU  - Michels, Birgitta
AU  - Neves, Esmeralda
AU  - Iracema Morais, Cátia
AU  - London, Jonathan
AU  - Mestrallet, Stéphanie
AU  - Quartier Dit Maire, Pierre
AU  - Neven, Bénédicte
AU  - Rapaport, Franck
AU  - Seeleuthner, Yoann
AU  - Lev, Atar
AU  - Simon, Amos J
AU  - Montoya, Jorge
AU  - Barel, Ortal
AU  - Gómez-Rodríguez, Julio
AU  - Orrego, Julio C
AU  - L'Honneur, Anne-Sophie
AU  - Soudée, Camille
AU  - Rojas, Jessica
AU  - Velez, Alejandra C
AU  - Sereti, Irini
AU  - Terrier, Benjamin
AU  - Marin, Nancy
AU  - García, Luis F
AU  - Abel, Laurent
AU  - Boisson-Dupuis, Stéphanie
AU  - Reis, Joel
AU  - Marinho, Antonio
AU  - Lisco, Andrea
AU  - Faria, Emilia
AU  - Goodnow, Christopher C
AU  - Vasconcelos, Julia
AU  - Béziat, Vivien
AU  - Ma, Cindy S
AU  - Somech, Raz
AU  - Casanova, Jean-Laurent
AU  - Bustamante, Jacinta
AU  - Franco, Jose Luis
AU  - Tangye, Stuart G
TI  - Helper T cell immunity in humans with inherited CD4 deficiency.
JO  - Journal of experimental medicine
VL  - 221
IS  - 5
SN  - 0022-1007
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DKFZ-2024-00641
SP  - e20231044
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38557723
DO  - DOI:10.1084/jem.20231044
UR  - https://inrepo02.dkfz.de/record/289207
ER  -