title: Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection.
abstract: OBJECTIVE
  To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1.
  
  
  METHODS
  This case-control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load.
  
  
  METHODS
  Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4 T cells.
  
  
  RESULTS
  Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4 and CD8 T cells in cord blood from cases compared with controls.
  
  
  CONCLUSIONS
  When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.
authors.affiliation: aSeattle Biomedical Research Institute bDepartment of Global Health cDepartment of Medicine dDepartment of Epidemiology eDepartment of Pediatrics, University of Washington fFred Hutchinson Cancer Research Center, Seattle, Washington, USA gCenter for Public Health Research, Kenya Medical Research Institute hDepartment of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Gasper
authors.forename: Pratima
authors.initials: P
authors.lastname: Kunwar
authors.forename: Grace
authors.initials: G
authors.lastname: Itaya
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lejarcegui
authors.forename: Rose
authors.initials: R
authors.lastname: Bosire
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.forename: Dalton
authors.initials: D
authors.lastname: Wamalwa
authors.forename: Jennifer
authors.initials: J
authors.lastname: Slyker
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007694:Killer Cells, Natural / Q000378:metabolism*; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D019562:Viral Load; D055815:Young Adult
references.citation: AIDS. 2012 Oct 23;26(16):2007-16
references.pmid: 22948269
references.citation: Immunol Rev. 2013 Jul;254(1):34-53
references.pmid: 23772613
references.citation: J Immunol. 2005 Nov 1;175(9):6117-22
references.pmid: 16237108
references.citation: Br J Haematol. 2009 Oct;147(2):185-91
references.pmid: 19796267
references.citation: J Infect Dis. 2009 Mar 15;199(6):889-98
references.pmid: 19434932
references.citation: J Clin Microbiol. 1999 Feb;37(2):350-3
references.pmid: 9889216
references.citation: PLoS One. 2013 Jun 21;8(6):e67700
references.pmid: 23805324
references.citation: AIDS. 2000 Nov 10;14(16):2535-41
references.pmid: 11101065
references.citation: Blood. 2005 Nov 15;106(10):3366-9
references.pmid: 16002429
references.citation: J Infect Dis. 2008 Feb 15;197(4):548-54
references.pmid: 18275275
references.citation: Immunology. 2009 Apr;126(4):458-65
references.pmid: 19278419
references.citation: J Clin Microbiol. 2000 Jul;38(7):2688-95
references.pmid: 10878065
references.citation: Haematologica. 1998 Mar;83(3):197-203
references.pmid: 9573672
references.citation: J Immunol. 2003 Dec 1;171(11):5663-7
references.pmid: 14634071
references.citation: J Virol. 1996 Sep;70(9):5799-806
references.pmid: 8709196
references.citation: AIDS. 2005 Nov 4;19(16):1849-55
references.pmid: 16227793
references.citation: Curr Opin HIV AIDS. 2010 Jul;5(4):291-7
references.pmid: 20543603
references.citation: AIDS. 2009 Sep 10;23(14):1807-15
references.pmid: 19584700
references.citation: Mucosal Immunol. 2012 Jan;5(1):30-40
references.pmid: 21993602
references.citation: J Infect Dis. 2010 Nov 1;202 Suppl 3:S339-44
references.pmid: 20887221
references.citation: Retrovirology. 2006 Jun 22;3:35
references.pmid: 16792805
references.citation: Bone Marrow Transplant. 1992;9 Suppl 1:64-7
references.pmid: 1504672
references.citation: Trends Immunol. 2001 Nov;22(11):633-40
references.pmid: 11698225
references.citation: PLoS Pathog. 2012;8(6):e1002739
references.pmid: 22719248
references.citation: J Immunol Methods. 2007 Apr 30;322(1-2):57-69
references.pmid: 17382342
references.citation: J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):209-15
references.pmid: 19504753
references.citation: Blood. 2010 Mar 18;115(11):2167-76
references.pmid: 19965656
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15011-6
references.pmid: 14645713
references.citation: AIDS Res Hum Retroviruses. 2004 Nov;20(11):1189-95
references.pmid: 15588341
references.citation: Cell Immunol. 1997 Sep 15;180(2):132-42
references.pmid: 9341743
references.citation: Lancet. 1999 Mar 6;353(9155):773-80
references.pmid: 10459957
references.citation: J Immunol. 2009 May 15;182(10):5914-8
references.pmid: 19414742
references.citation: J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):138-42
references.pmid: 15905728
references.citation: Curr HIV Res. 2013 Jan;11(1):10-23
references.pmid: 23305198
references.citation: J Infect Dis. 2010 Sep 15;202(6):899-907
references.pmid: 20687848
references.citation: J Infect Dis. 2007 Jan 15;195(2):220-9
references.pmid: 17191167
references.citation: Retrovirology. 2006 Aug 17;3:52
references.pmid: 16916447
references.citation: Nat Genet. 2007 Jun;39(6):733-40
references.pmid: 17496894