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Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life.


ABSTRACT: Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. In this article, we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. Whereas adult CD8+ T cells differentiated into a heterogeneous pool of effector and memory cells, neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and exhibited a distinct gene expression profile. Surprisingly, impaired neonatal memory formation was not due to a lack of responsiveness, but instead because neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became terminally differentiated. Collectively, these findings demonstrate that neonatal CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell differentiation, which impairs the formation of memory CD8+ T cells in early life.

SUBMITTER: Smith NL 

PROVIDER: S-EPMC4065808 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life.

Smith Norah L NL   Wissink Erin E   Wang Jocelyn J   Pinello Jennifer F JF   Davenport Miles P MP   Grimson Andrew A   Rudd Brian D BD  

Journal of immunology (Baltimore, Md. : 1950) 20140521 1


Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. In this article, we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. Whereas adult CD8+ T cells differentiated i  ...[more]

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