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

Brian D. Rudd, Vanessa Venturi, Norah L. Smith, Kito Nzingha, Emily L. Goldberg, Gang Li, Janko Nikolich-Zugich, Miles P. Davenport

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1003572
JournalPLoS Pathogens
Volume9
Issue number9
DOIs
StatePublished - Sep 2013

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T-Lymphocytes
Infection
Virus Replication
Immunity
Vaccination
Antigen Receptors
Aptitude
Human Development
Immune System
Lymphocytes
Antigens

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Rudd, B. D., Venturi, V., Smith, N. L., Nzingha, K., Goldberg, E. L., Li, G., ... Davenport, M. P. (2013). Acute Neonatal Infections 'Lock-In' a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses. PLoS Pathogens, 9(9), [e1003572]. https://doi.org/10.1371/journal.ppat.1003572

Acute Neonatal Infections 'Lock-In' a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses. / Rudd, Brian D.; Venturi, Vanessa; Smith, Norah L.; Nzingha, Kito; Goldberg, Emily L.; Li, Gang; Nikolich-Zugich, Janko; Davenport, Miles P.

In: PLoS Pathogens, Vol. 9, No. 9, e1003572, 09.2013.

Research output: Contribution to journalArticle

Rudd, Brian D. ; Venturi, Vanessa ; Smith, Norah L. ; Nzingha, Kito ; Goldberg, Emily L. ; Li, Gang ; Nikolich-Zugich, Janko ; Davenport, Miles P. / Acute Neonatal Infections 'Lock-In' a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses. In: PLoS Pathogens. 2013 ; Vol. 9, No. 9.
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