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

• Published in: The Journal of immunology (1950) Vol. 193; no. 1; pp. 177 - 184
• Main Authors: Smith, Norah L, Wissink, Erin, Wang, Jocelyn, Pinello, Jennifer F, Davenport, Miles P, Grimson, Andrew, Rudd, Brian D
• Format: Journal Article
• Language: English
• Published: United States 01.07.2014
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Proliferation; Immunologic Memory - physiology; Mice; Mice, Transgenic
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1400553

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.