title: Fetal exposure to HIV-1 alters chemokine receptor expression by CD4+T cells and increases susceptibility to HIV-1.
abstract: Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord blood CD4(+) T cells from HIV-1-exposed children and healthy controls. At baseline CD4(+) T cells had a largely naïve phenotype. However, stimulation with cytokines resulted in an upregulation of inflammatory response-related chemokine receptors on CD4(+) T cells, with HIV-1-exposed infants having a significantly higher frequency of CD4(+) T cells expressing, in particularly Th2 associated chemokine receptors (CCR3 p < 0.01, CCR8 p = 0.03). Numbers of naive CCR7(+) CD4(+) T cells were reduced (p = 0.01) in HIV-1-exposed infants. We further assessed whether the inflammatory phenotype was associated with susceptibility to HIV-1 and detected higher levels of p24 upon in in vitro infection of stimulated CD4(+) T cells of HIV-1-exposed infants. In summary, fetal exposure to HIV-1 primes the immune system in the infant leading to an enhanced immune activation and altered T cell homing, with potential ramifications regarding T cell responses and the acquisition of HIV-1 as an infant.
authors.affiliation: 1] Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands [2] Department of Experimental Immunology, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Bunders
authors.affiliation: 1] Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands [2] Department of Experimental Immunology, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: John L
authors.initials: JL
authors.lastname: van Hamme
authors.affiliation: 1] Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands [2] Department of Experimental Immunology, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Machiel H
authors.initials: MH
authors.lastname: Jansen
authors.affiliation: Department of Obstetrics, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Boer
authors.affiliation: Department of Experimental Immunology, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.affiliation: 1] Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands [2] Department of Experimental Immunology, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D010641:Phenotype; D011247:Pregnancy; D019707:Receptors, Chemokine / Q000235:genetics*
chemical_list: D019707:Receptors, Chemokine