University of Cambridge > Talks.cam > Departmental Seminar Programme, Department of Veterinary Medicine > LYMPHOPOIESIS IN THE FOETUS AND NEONATE

LYMPHOPOIESIS IN THE FOETUS AND NEONATE

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The foetus develops in a protected intrauterine environment where the onus is largely on non responsiveness. At birth a major physiological event occurs whereby the newborn undergoes a transition from its protected environment to one where pathogenic organisms are encountered for the first time and protection is vital. Considering the importance of neonatal immune competency in influencing predisposition to infection and possibly allergies surprisingly little attention has been paid to how the immune system adapts to these changed circumstances. In the foetus and neonate the naïve T cell pool rapidly expands as the animals grow but the mechanisms that regulate this T cell homeostasis are poorly understood. Using the tracking dye CFSE in vivo in combination with flow cytometry we have been able to measure the phenotypes and number of T cells exported from the foetal and neonatal lamb thymus and their distribution and lifespan in peripheral tissues. This has been coupled to peripheral T cell division using whole body or site specific labelling of T cells with BrdU and death of cells as measured by using Annexin V. Major differences were found in the rate of thymic export and homing specificities of distinct |T cells subsets during foetal and neonatal life. Moreover the numbers of T cells produced each day by thymic export and substantial clonal expansion in peripheral lymphoid tissues in both the foetus and neonate were well in excess of those needed for the growth of the peripheral T cell pool. Our results show that newly produced T cells (particulary those in the recirculating T cell pool) have an extremely short lifespan, and are replaced by fresh waves of clonally expanding thymic emigrants. Continuous displacement of short-lived naïve recirculating T cell populations by clonally expanding thymic emigrants is likely to confer an important survival advantages on the neonate through the regular reconstitution of a substantial portion of the naïve peripheral T cell repertoire for antigen.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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