Ontogeny of CD4+ t lymphocytes with phenotypic susceptibility to HIV-1 during exclusive and nonexclusive breastfeeding in HIV-1-exposed ugandan infants

Elizabeth J. McFarland, Tina M. Powell, Carolyne Onyango-Makumbi, Weiming Zhang, Kelsey Melander, Prossy Naluyima, Samuel Okurut, Michael A. Eller, Mary Glenn Fowler, Edward N. Janoff

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
JournalJournal of Infectious Diseases
Volume215
Issue number3
DOIs
StatePublished - 2017

Keywords

  • Breastfeeding
  • CCR5
  • CD4+ T lymphocytes
  • HIV-1
  • Lymphocyte activation
  • Postnatal transmission
  • T cell homing
  • α4β7

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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  • Cite this

    McFarland, E. J., Powell, T. M., Onyango-Makumbi, C., Zhang, W., Melander, K., Naluyima, P., Okurut, S., Eller, M. A., Fowler, M. G., & Janoff, E. N. (2017). Ontogeny of CD4+ t lymphocytes with phenotypic susceptibility to HIV-1 during exclusive and nonexclusive breastfeeding in HIV-1-exposed ugandan infants. Journal of Infectious Diseases, 215(3), 368-377. https://doi.org/10.1093/infdis/jiw553