TY - JOUR
T1 - Ontogeny of CD4+ t lymphocytes with phenotypic susceptibility to HIV-1 during exclusive and nonexclusive breastfeeding in HIV-1-exposed ugandan infants
AU - McFarland, Elizabeth J.
AU - Powell, Tina M.
AU - Onyango-Makumbi, Carolyne
AU - Zhang, Weiming
AU - Melander, Kelsey
AU - Naluyima, Prossy
AU - Okurut, Samuel
AU - Eller, Michael A.
AU - Fowler, Mary Glenn
AU - Janoff, Edward N.
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society.
PY - 2017
Y1 - 2017
N2 - Background. Among infants exposed to human immunodeficiency virus (HIV) type 1, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. Methods. HIV-1-exposed Ugandan infants were prospectively assessed during the first year of life for feeding practices and T-cell maturation, intestinal homing (β7hi), activation, and HIV-1 coreceptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods before 6 months were categorized as exclusive and nonexclusive, respectively. Results. Among CD4+ and CD8+ T cells, the expression of memory, activation, and CCR5 markers increased rapidly from birth to week 2, peaking at week 6, whereas cells expressing the intestinal homing marker increased steadily in the central memory (CM) and effector memory T cells over 48 weeks. At 24 weeks, when feeding practices had diverged, nonexclusively breastfed infants showed increased frequencies and absolute counts of β7hi CM CD4+ and CD8+ T cells, including the HIV-1-targeted cells with CD4+β7hi/CCR5+ coexpression, as well as increased activation. Conclusions. The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.
AB - Background. Among infants exposed to human immunodeficiency virus (HIV) type 1, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. Methods. HIV-1-exposed Ugandan infants were prospectively assessed during the first year of life for feeding practices and T-cell maturation, intestinal homing (β7hi), activation, and HIV-1 coreceptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods before 6 months were categorized as exclusive and nonexclusive, respectively. Results. Among CD4+ and CD8+ T cells, the expression of memory, activation, and CCR5 markers increased rapidly from birth to week 2, peaking at week 6, whereas cells expressing the intestinal homing marker increased steadily in the central memory (CM) and effector memory T cells over 48 weeks. At 24 weeks, when feeding practices had diverged, nonexclusively breastfed infants showed increased frequencies and absolute counts of β7hi CM CD4+ and CD8+ T cells, including the HIV-1-targeted cells with CD4+β7hi/CCR5+ coexpression, as well as increased activation. Conclusions. The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.
KW - Breastfeeding
KW - CCR5
KW - CD4+ T lymphocytes
KW - HIV-1
KW - Lymphocyte activation
KW - Postnatal transmission
KW - T cell homing
KW - α4β7
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U2 - 10.1093/infdis/jiw553
DO - 10.1093/infdis/jiw553
M3 - Article
C2 - 27932619
AN - SCOPUS:85019874443
SN - 0022-1899
VL - 215
SP - 368
EP - 377
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -