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Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to child transmission of HIV-1.
MedLine Citation:
PMID:  23033270     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Despite potential clinical importance, target cells for HIV-1 in mother-to child-transmission (MTCT) have not yet been identified. Cord blood-derived CD4(+) T cells are largely naïve and do not express CCR5, the mandatory co-receptor for transmitted HIV-1 R5 strains in infants. Here, we demonstrate that in the human fetal and infant gut mucosa there is already a large subset of mucosal memory CD4(+)CCR5(+) T cells with predominantly a Th1 and Th17 phenotype. Using next-generation sequencing of the T-cell-receptor β chain, clonally expanded T cells, as a hallmark for memory development predominated in the gut mucosa (30%), while few were found in lymph node (1%) and none in cord blood (0%). The gut mucosal fetal and infant CD4(+) T cells were highly susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected PHA stimulated adult PBMCs. In conclusion, we show that extensive adaptive immunity is present before birth, with the gut mucosa as the preferential site for memory CD4(+) T cells. These CD4(+)CCR5(+) T cells in the infant mucosa provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of MTCT, which can be targeted in prevention strategies.
Authors:
Madeleine J Bunders; Chris M van der Loos; Paul L Klarenbeek; John L van Hamme; Kees Boer; Jim C H Wilde; Niek de Vries; Rene A W van Lier; Neeltje Kootstra; Steven T Pals; Taco W Kuijpers
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam (UvA), Amsterdam, Netherlands;
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