Journal Article

DKFZ-2024-00641

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Helper T cell immunity in humans with inherited CD4 deficiency.

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. T. ; Rao, G. ; Waterboer, T.DKFZ* ; Michels, B.DKFZ* ; Neves, E. ; Iracema Morais, C. ; London, J. ; Mestrallet, S. ; Quartier Dit Maire, P. ; Neven, B. ; Rapaport, F. ; Seeleuthner, Y. ; Lev, A. ; Simon, A. J. ; Montoya, J. ; Barel, O. ; Gómez-Rodríguez, J. ; Orrego, J. C. ; L'Honneur, A.-S. ; Soudée, C. ; Rojas, J. ; Velez, A. C. ; Sereti, I. ; Terrier, B. ; Marin, N. ; García, L. F. ; Abel, L. ; Boisson-Dupuis, S. ; Reis, J. ; Marinho, A. ; Lisco, A. ; Faria, E. ; Goodnow, C. C. ; Vasconcelos, J. ; Béziat, V. ; Ma, C. S. ; Somech, R. ; Casanova, J.-L. ; Bustamante, J. ; Franco, J. L. ; Tangye, S. G.

2024
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi: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.

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Contributing Institute(s):

1. Infektionen und Krebs-Epidemiologie (F020)
2. Infektionen und Krebs-Epidemiologie (D320)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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