Phenotype of T cells, their soluble receptor levels, and cytokine profile of human breast milk.

Human breast milk has important immunoprotective and immunosuppressive functions for an infant. The purpose of this study was to extend the phenotype of milk cells and to measure soluble T cell receptor levels and cytokines in milk, and to compare these with neonatal and adult blood. Milk T cells had a more equivalent CD4:CD8 ratio than blood; milk CD4 T cells mainly expressed the CD45RO (antigen primed/memory) phenotype; milk CD8 cells had an equivalent CD11b:CD28 suppressor:cytotoxic phenotype; and milk T cells had 2-3-fold higher percentages of activated CD4 IL-2R and CD8 HML-1 or CD8 VLA-1 cells than blood. Soluble IL-2R, CD4 and CD8 concentrations were lower in milk than adult blood, although relatively increased when compared to the lower T cell concentration in milk. Breast milk contained high levels of IFN-gamma but low levels of other measured cytokines compared to blood. These distinct differences of T cells and their soluble products are likely to influence an infant's immune system.

Immune activation during infancy in healthy humans.

Immune activity during infancy was investigated using blood samples from 30 neonates and 52 healthy infants between 2 and 15 months of age attending for immunization. The purpose of this study was to assess the total immune activity of T cells using soluble interleukin-2 receptor (IL-2R) and interferon-gamma concentrations. These were compared with the proportion of CD4 CD45RO-, IL-2R (CD25)-, and transferrin receptor (CD71)-positive peripheral blood lymphocytes. The median duration of breast-feeding and of introduction of solid feeds was 4.2 and 4.0 months, respectively. Compared to neonates, the mean +/- SE soluble IL-2R concentration peaked at 4 months of age (1670 +/- 94 vs 3060 +/- 252 U/ml; P < 0.0001), as did pooled interferon-gamma levels. The percentage of CD4 CD45RO T cells remained low and the proportion of activated peripheral blood lymphocytes decreased during infancy. We conclude that noncirculatory immune activity is increased during infancy and this is associated with weaning.

Phenotype and activation of milk-derived and peripheral blood lymphocytes from normal and coeliac subjects.

The phenotype of milk-derived and peripheral blood lymphocytes from normal and coeliac subjects was assessed for CD3, alpha beta-TcR (T cell receptor), gamma delta-TcR, CD4, CD8, HML-1 (human mucosal lymphocyte) determinants, and activation was measured by interleukin-2 receptor (IL-2R) expression. Milk cells from normal and coeliac subjects were analysed by manual immunofluorescence and milk and blood cells from normal subjects were analysed by flow cytometry. Milk cells from two coeliac subjects were tested for proliferation to gluten antigen. The CD4:CD8 ratio of milk lymphocytes from both normal and coeliac subjects was similar (0.78-1.1), but lower than that present in blood (1.5-2.1). The IL-2R expression of milk lymphocytes from both coeliac and normal subjects was increased by 3-6 times compared with peripheral blood cells. For example, IL-2R was present on 27.3% of milk CD3+ lymphocytes and on 8.0% of blood CD3+ lymphocytes from normal subjects. gamma delta- and HML-1+ T cells were increased 4.2-fold and 12-fold respectively compared with blood lymphocytes. Milk cells from coeliac subjects showed specific proliferation to gluten but not to soya bean antigen. We conclude that milk cells have a 'mucosal' phenotype, with increased gamma delta-TcR, CD8+ and HML-1+ T cells, and have an increased proportion of activated cells. Milk cells from coeliac subjects have no 'toxic' phenotype, but show functional reactivity by specific proliferation to gluten antigen.