title: Memory CD4(+)CCR5(+) T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1.
abstract: Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, 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 TCRβ chain, clonally expanded T cells as a hallmark for memory development predominated in the gut mucosa (30%), whereas few were found in the lymph nodes (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 phytohemagglutinin-stimulated adult PBMCs. In conclusion, in the present study, we show that extensive adaptive immunity is present before birth and the gut mucosa is 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 mother-to-child transmission that can be targeted in prevention strategies.
authors.affiliation: Departments of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children’s Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. m.j.bunders@amc.uva.nl
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Bunders
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Paul L
authors.initials: PL
authors.lastname: Klarenbeek
authors.forename: John L
authors.initials: JL
authors.lastname: van Hamme
authors.forename: Kees
authors.initials: K
authors.lastname: Boer
authors.forename: Jim C H
authors.initials: JC
authors.lastname: Wilde
authors.forename: Niek
authors.initials: N
authors.lastname: de Vries
authors.forename: Rene A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Neeltje
authors.initials: N
authors.lastname: Kootstra
authors.forename: Steven T
authors.initials: ST
authors.lastname: Pals
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology* / Q000821:virology; D008297:Male; D009034:Mother-Child Relations; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism*
chemical_list: D019713:Receptors, CCR5