title: Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T-cell differentiation and modulates responses to Bacille Calmette-Guérin (BCG) vaccine in HIV-uninfected infants.
abstract: Human immunodeficiency virus (HIV)-negative infants born to HIV-positive mothers frequently exhibit a range of immunological abnormalities. We tested the hypothesis that HIV during pregnancy affects the ability of CD4 T cells of HIV-negative infants to respond to vaccine challenge by recruiting HIV-negative infants born to HIV-negative and HIV-positive mothers and measuring their responses to Bacille Calmette-Guérin (BCG) vaccine given at birth. At 2 weeks, maternal HIV status did not influence CD4 T-cell counts or differentiation, but by 10 weeks CD4 counts of infants born to HIV-positive mothers fell to a level characteristic of HIV-positive infants. Among the CD4 T-cell populations, markers of differentiation (CCR7(-) CD45RA(-) CD27(-)) and senescence (CD57, PD-1) were more common among infants born to HIV-positive mothers than among infants born to HIV-negative mothers. At 2 weeks of age, we assessed the effector response to heat-killed BCG and tuberculin purified protein derivative (PPD) by overnight interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming cell assay (ELISpot), but found no measurable effect of maternal HIV status. At 10 weeks, we assessed CD4 T-cell memory by measuring proliferation in response to the same antigens. We observed a bimodal response that allowed infants to be classified as high or low responders and found that fewer infants born to HIV-positive mothers were able to mount a robust proliferative response, suggesting that their reduced CD4 counts and increased differentiation indicated a deficiency in their ability to develop immunological memory.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Chichiri, Blantyre, Malawi. d.j.c.miles@gmail.com
authors.forename: David J C
authors.initials: DJ
authors.lastname: Miles
authors.forename: Louis
authors.initials: L
authors.lastname: Gadama
authors.forename: Anita
authors.initials: A
authors.lastname: Gumbi
authors.forename: Flora
authors.initials: F
authors.lastname: Nyalo
authors.forename: Bonus
authors.initials: B
authors.lastname: Makanani
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001034:Apgar Score; D001500:BCG Vaccine / Q000276:immunology*; D001724:Birth Weight; D049628:Body Size; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011051:Poliomyelitis / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D054400:Receptors, CCR7 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology; D014470:Umbilical Cord / Q000276:immunology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D001500:BCG Vaccine; C515370:CCR7 protein, human; D007074:Immunoglobulin G; D054400:Receptors, CCR7; D014373:Tuberculin; D007371:Interferon-gamma