Impact of fetal/post-natal undernutrition on thymic development and the post-natal maturation and homeostasis of naïve T-cells and B-cells

Fetal T-cell and B-cell development begins at the end of the first trimester, with a rapid expansion of cell numbers through early childhood. This expansion involves the de novo production and export by the thymus of transitional T-cells (recent thymic emigrants; RTE), which then mature into naïve cells in the periphery. Understanding the impact of early nutrition on thymic development has been a major focus of ING’s research endeavours over recent years. However, the critical limitation of all these previous studies is the lack of any direct data on thymic function or output. Based on existing evidence of effects on thymic size, we hypothesise that insults during critical windows of development will reduce the structure and/or function of the thymus, permanently altering specific cell populations, and leading to subsequent immune-deficiencies. Further, we hypothesise that early nutritional interventions will reverse these perturbations. This will be tested through the ENID Trial data. In collaboration with Professor David Lewis and the Lewis Lab at Stanford University, we have been awarded a 5y programme grant from the National Institute of Allergy and Infectious Diseases (NIAID) to use the ENID Trial to look at ‘Transitional and naïve CD4 T cells and B cells in infant vaccine responses’.

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