Prolonged exclusive breastfeeding reduces autoimmune diabetes incidence and increases regulatory T-cell frequency in bio-breeding diabetes-prone rats

Background Previously, we reported that exclusive breastfeeding delayed and partially protected bio-breeding diabetes-prone (BBDP) rats from spontaneous autoimmune diabetes development. To investigate whether this protection results from modulation of the (mucosal) immune system, the present study was designed to analyse the effect of nutrition early in life on the immune status of BBDP rats.Methods The breastfeeding period of BBDP pups was extended or not, while allowing half of the pups to eat during that period whereas the other half received only breast milk. Cytokine profiles as well as naturally occurring regulatory T-cell frequencies were measured over time in the mesenteric lymph nodes (MLNs) and spleen.Results Prolonged exclusive breastfeeding partially protects against autoimmune diabetes development and resulted in elevated levels of natural regulatory T cells (CD4(+) CD25(+) FoxP3(+)) in MLNs and spleen directly after weaning and throughout life. Stimulation of MLN cells from rats that ingested solid food during the nursing period showed massive secretion of interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10, whereas MLN cells from exclusive breastfed rats did not. In contrast, transforming growth factor beta (TGF-beta) was secreted equally by all groups.Conclusions Prolonged exclusive breastfeeding partially protects BBDP rats from autoimmune diabetes development. Interestingly, ingestion of solid food during the weaning period completely abolishes this protective effect. The protective effect of exclusive breastfeeding correlates with higher levels of naturally occurring regulatory T cells throughout life and low cytokine secretion at weaning. Copyright (C) 2009 John Wiley & Sons, Ltd.