Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts

Deepa Rai; Nhat-Long L Pham; John T Harty; Vladimir P Badovinac

doi:10.4049/jimmunol.0902874

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Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts

Journal article

Peer reviewed

Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts

Deepa Rai, Nhat-Long L Pham, John T Harty and Vladimir P Badovinac

The Journal of immunology (1950), Vol.183(12), pp.7672-7681

12/15/2009

DOI: 10.4049/jimmunol.0902874

PMCID: PMC2808048

PMID: 19933864

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Abstract

Determining the magnitude and kinetics, together with the phenotypic and functional characteristics of responding CD8 T cells, is critical for understanding the regulation of adaptive immunity as well as in evaluating vaccine candidates. Recent technical advances have allowed tracking of some CD8 T cells responding to infection, and a body of information now exists describing phenotypic changes that occur in CD8 T cells of known Ag-specificity during their activation, expansion, and memory generation in inbred mice. In this study, we demonstrate that Ag but not inflammation-driven changes in expression of CD11a and CD8alpha can be used to distinguish naive from Ag-experienced (effector and memory) CD8 T cells after infection or vaccination. Interestingly and in contrast to inbred mice, tracking polyclonal CD8 T cell responses with this approach after bacterial and viral infections revealed substantial discordance in the magnitude and kinetics of CD8 T cell responses in outbred hosts. These data reveal limitations to the use of inbred mouse strains as preclinical models at vaccine development and suggest the same dose of infection or vaccination can lead to substantial differences in the magnitude and timing of Ag-specific CD8 expansion as well in differences in protective memory CD8 T cell numbers in outbred individuals. This concept has direct relevance to development of vaccines in outbred humans.

Lymphocytic Choriomeningitis - immunology

Lymphoid Tissue - immunology

Lymphocytic Choriomeningitis - metabolism

Lymphocyte Activation - immunology

Listeriosis - immunology

CD8-Positive T-Lymphocytes - metabolism

Clone Cells

CD11a Antigen - metabolism

CD11a Antigen - biosynthesis

Biomarkers - metabolism

Listeriosis - metabolism

CD8-Positive T-Lymphocytes - microbiology

Lymphocytic Choriomeningitis - pathology

Lymphoid Tissue - virology

Mice, Inbred C57BL

Lymphoid Tissue - metabolism

Mice, Transgenic

Viral Vaccines - administration & dosage

CD8 Antigens - metabolism

Animals

Bacterial Vaccines - administration & dosage

Bacterial Vaccines - immunology

Epitopes, T-Lymphocyte - physiology

Up-Regulation - immunology

CD8-Positive T-Lymphocytes - virology

Down-Regulation - immunology

Listeriosis - pathology

Immunologic Memory

Mice

Mice, Inbred BALB C

Lymphoid Tissue - microbiology

CD8-Positive T-Lymphocytes - immunology

Viral Vaccines - immunology

Epitopes, T-Lymphocyte - metabolism

Details

Title: Subtitle: Tracking the total CD8 T cell response to infection reveals substantial discordance in magnitude and kinetics between inbred and outbred hosts
Creators: Deepa Rai - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Nhat-Long L Pham
John T Harty
Vladimir P Badovinac
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.183(12), pp.7672-7681
DOI: 10.4049/jimmunol.0902874
PMID: 19933864
PMCID: PMC2808048
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI050073 / NIAID NIH HHS R01 AI083286-01 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS AI42767 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS AI83286 / NIAID NIH HHS AI50073 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R01 AI046653 / NIAID NIH HHS AI59752 / NIAID NIH HHS R01 AI059752 / NIAID NIH HHS AI46653 / NIAID NIH HHS
Language: English
Date published: 12/15/2009
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047862402771

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