Diverse CD8 T Cell Responses to Viral Infection Revealed by the Collaborative Cross

Cell Rep. 2020 Apr 14;31(2):107508. doi: 10.1016/j.celrep.2020.03.072.

Abstract

Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit for the high degree of genetic variation present, because it allows for assessment of genetic factors underlying unique phenotypes. Here, we advance the utility of the CC as a tool to analyze the immune response to viral infection. We describe variability in resting immune cell composition and adaptive immune responses generated among CC strains following systemic virus infection and reveal quantitative trait loci responsible for generation of CD62L+ memory CD8 T cells.

Keywords: CD8 T cells; QTL mapping; central memory; collaborative cross; immunological memory; mouse models.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Crosses, Genetic
  • Female
  • Genetic Variation / genetics
  • Genotype
  • Haplotypes / genetics
  • Immunologic Memory / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Models, Immunological
  • Phenotype
  • Quantitative Trait Loci / genetics
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Virus Diseases / genetics