Document Type
Article
Publication Date
5-6-2024
Original Citation
Guérin A,
Moncada-Vélez M,
Jackson K,
Ogishi M,
Rosain J,
Mancini M,
Langlais D,
Nunez A,
Webster S,
Goyette J,
Khan T,
Marr N,
Avery D,
Rao G,
Waterboer T,
Michels B,
Neves E,
Iracema Morais C,
London J,
Mestrallet S,
Quartier Dit Maire P,
Neven B,
Rapaport F,
Seeleuthner Y,
Lev A,
Simon A,
Montoya J,
Barel O,
Gómez-Rodríguez J,
Orrego J,
L'Honneur A,
Soudée C,
Rojas J,
Velez A,
Sereti I,
Terrier B,
Marin N,
García L,
Abel L,
Boisson-Dupuis S,
Reis J,
Marinho A,
Lisco A,
Faria E,
Goodnow C,
Vasconcelos J,
Béziat V,
Ma C,
Somech R,
Casanova J,
Bustamante J,
Franco J,
Tangye S.
Helper T cell immunity in humans with inherited CD4 deficiency. J Exp Med. 2024;221(5):e20231044.
Keywords
JGM, Humans, T-Lymphocytes, Helper-Inducer, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Lymphocyte Activation, HLA Antigens, Protein Isoforms
JAX Source
J Exp Med. 2024;221(5):e20231044.
ISSN
1540-9538
PMID
38557723
DOI
https://doi.org/10.1084/jem.20231044
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.
Comments
© 2024 Guérin et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/)