Acute Neonatal Infections ‘Lock-In’ a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses

PLoS Pathogens

Miles P. Davenport¹  Vanessa Venturi²  Gang Li³  Janko Nikolich-Zugich³  Emily L. Goldberg³  Kito Nzingha⁴  Brian D. Rudd⁴  Norah L. Smith⁴ 

[1] Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia;Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia;Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, and the BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America;Department of Microbiology and Immunology, Cornell University, Ithaca, New York, United States of America

关键词: T cells;    Cytotoxic T cells;    Memory T cells;    Neonates;    Immune response;    Vaccination;    immunization;    Memory;    Recall (memory);   

DOI  :  10.1371/journal.ppat.1003572

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in the immune compartment and functional immunity remain unclear. The ability of the immune system to respond to specific antigens and mediate protection in early life is closely correlated with the level of diversification of lymphocyte antigen receptors. We have previously shown that the neonatal primary CD8+ T cell response to replication competent virus is significantly constricted compared to the adult response. In the present study, we have analyzed the subsequent formation of neonatal memory CD8+ T cells and their response to secondary infectious challenge. In particular, we asked whether the less diverse CD8+ T cell clonotypes that are elicited by neonatal vaccination with replication competent virus are ‘locked-in’ to the adult memory T cell, and thus may compromise the strength of adult immunity. Here we report that neonatal memory CD8+ T cells mediate poor recall responses compared to adults and are comprised of a repertoire of lower avidity T cells. During a later infectious challenge the neonatal memory CD8+ T cells compete poorly with the fully diverse repertoire of naïve adult CD8+ T cells and are outgrown by the adult primary response. This has important implications for the timing of vaccination in early life.

【 授权许可】

CC BY