Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding

J Immunol. 2009 Oct 1;183(7):4322-8. doi: 10.4049/jimmunol.0900829. Epub 2009 Sep 4.


The ontogeny of the immune system and the effect thereon by type of infant feeding is incompletely understood. We analyzed frequencies and composition of immune cells in blood of breastfed (BF) and formula-fed (FF) infants at 1.5, 4, and 6 mo of age. Three formulas with the same protein concentration but with varying levels of alpha-lactalbumin and caseinoglycomacropeptide were compared. Twenty-nine exclusively BF infants served as reference, and 17 infants in each formula group completed the study. Whole blood and PBMCs were analyzed by flow cytometry and immunoflow cytometry, respectively. Leukocyte count of BF infants increased with time due to increased frequency of neutrophils. Lymphocyte count was high at 1.5 mo and was unchanged over time, as were the relative proportions of CD4+ alphabetaT cells, CD8+ alphabetaT cells, B cells, NK cells, and gammadeltaT cells. Most CD45R0+CD3+ cells were HLA-DR- and hence memory cells. Compared with breastfeeding, formula feeding resulted in a significant decrease in proportion of NK cells, but a significant increase in naive CD4+ alphabetaT cells and an elevated CD4-to-CD8 ratio, that is, 3.3 in the combined FF groups compared with 2.6 in the BF group. No significant differences were found between the three groups of FF infants. In conclusion, blood cells of lymphoid lineage did not change significantly in frequencies or composition from 1.5 to 6 mo of age in BF infants. In contrast, FF infants displayed an ongoing maturation of adaptive immunity cells and a delayed recruitment of innate immunity cells as compared with BF infants.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Feeding*
  • Caseins / administration & dosage
  • Down-Regulation / immunology
  • Female
  • Follow-Up Studies
  • Glycopeptides / administration & dosage
  • Glycopeptides / physiology
  • Humans
  • Immunity, Innate
  • Immunophenotyping
  • Infant
  • Infant Formula*
  • Lactalbumin / administration & dosage
  • Lactalbumin / biosynthesis
  • Lactalbumin / pharmacology
  • Lactoglobulins / administration & dosage
  • Lactoglobulins / antagonists & inhibitors
  • Lactoglobulins / physiology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism*
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Prospective Studies
  • Up-Regulation / immunology


  • Caseins
  • Glycopeptides
  • Lactoglobulins
  • kappa-casein glycomacropeptide
  • Lactalbumin