Does breastfeeding affect the infant's immune responsiveness?

Breastfeeding, the natural feeding mode, has beneficial effects on the nutritional status of the infant, but also protects against a range of infections, and infection-related diseases, such as sepsis, pneumonia, otitis media, urinary tract infection, diarrhoea, and necrotizing enterocolitis (1). Although we do not know the mechanism of protection, a modulation of the infant’s microbiology, physiology and perhaps immunology may be involved. The paper by Pabst et al. in a recent issue of Acta Paediatrica (2) deals with the question whether breastand bottle-fed infants differ with respect to spontaneous and vaccine-induced lymphocyte activation. First, three small groups of 6-month-old infants, breastfed, bottle-fed and mixed-fed, were examined for the expression of integrins on peripheral blood lymphocytes. The CD4and CD8-positive T lymphocytes of the breastfed infants expressed lower levels of the integrin moleculesb1, a4, a5 anda6 than did the lymphocytes of bottle-fed infants. Mixed-fed infants were intermediate in T cell integrin expression. The same pattern was seen for the b1, a4, a6, RHAMN and CD38 integrins on CD19-positive cells, i.e. B lymphocytes. The differences in integrin expression were substantial and consistent, and indicate that circulating lymphocytes from bottle-fed infants are more often activated than those of breastfed infants. A second larger cohort of breastand bottle-fed infants was studied at 12 months of age. It is not clear if they were still breastfed by the time of the study, but both groups received additional solid feeds. First, blood lymphocytes were stimulated with tetanus toxoid or Candidaantigen and their proliferative response and interferong production was measured. Lymphocytes from breastfed infants displayed lower proliferative responses and interferong production at base-line and when stimulated with tetanus toxoid or Candida. The cohort was then vaccinated with live attenuated measles–mumps–rubella (MMR) virus. The breastfed infants exhibited marginally lower neutralizing antibody titres to measles virus than the bottle-fed infants after vaccination, as well as a somewhat lower proliferative response to measles virus haemagglutinin. Breastfed but not bottle-fed infants showed a transient increase in CD8and CD56-positive cell numbers in the blood, i.e. cytotoxic T cells and NK cells. When leukocytes from breastand bottle-fed infants were stimulated with the mitogen PHA, there was a tendency towards increased IFN-g production in leukocytes derived from breastfed infants as compared to those from bottle-fed infants, whereas the IL-4 and IL-10 production was similar in the two groups. The data clearly demonstrate that the base-line activation of lymphocytes is higher in bottle-fed than in breastfed infants, as reflected by a higher integrin expression and proliferative response in the absence of antigen. This activation could be the result of the exposure of bottle-fed infants to a larger variety of foreign food proteins. It is, owever, unlikely that simple food antigens would give rise to such a marked and persistent lymphocyte activation. At least two other possibilities should be considered: First, the presence of anti-inflammatory/anti-proliferative factors in breast milk could decrease the activation of the immune system of the breastfed infant. Secondly, the bottle-fed infant could have a more varied intestinal microflora and be exposed to a greater variety of microbial products capable of stimulating the immune system. The two possibilities are, of course, not mutually exclusive.