Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge

Javier Cabrera-Perez; Stephanie A Condotta; Britnie R James; Sakeen W Kashem; Erik L Brincks; Deepa Rai; Tamara A Kucaba; Vladimir P Badovinac; Thomas S Griffith

doi:10.4049/jimmunol.1401711

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Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge

Journal article

Peer reviewed

Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge

Javier Cabrera-Perez, Stephanie A Condotta, Britnie R James, Sakeen W Kashem, Erik L Brincks, Deepa Rai, Tamara A Kucaba, Vladimir P Badovinac and Thomas S Griffith

The Journal of immunology (1950), Vol.194(4), pp.1609-1620

02/15/2015

DOI: 10.4049/jimmunol.1401711

PMCID: PMC4412277

PMID: 25595784

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Abstract

Patients surviving the acute stages of sepsis develop compromised T cell immunity and increased susceptibility to infection. Little is known about the decreased CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous Ag-specific CD4 T cell populations after cecal ligation and puncture-induced sepsis and analyzed the CD4 T cell response to heterologous infection during or after recovery. We observed that the sepsis-induced early loss of CD4 T cells was followed by thymic-independent numerical recovery in the total CD4 T cell compartment. Despite this numerical recovery, we detected alterations in the composition of naive CD4 T cell precursor pools, with sustained quantitative reductions in some populations. Mice that had experienced sepsis and were then challenged with epitope-bearing, heterologous pathogens demonstrated significantly reduced priming of recovery-impaired Ag-specific CD4 T cell responses, with regard to both magnitude of expansion and functional capacity on a per-cell basis, which also correlated with intrinsic changes in Vβ clonotype heterogeneity. Our results demonstrate that the recovery of CD4 T cells from sepsis-induced lymphopenia is accompanied by alterations to the composition and function of the Ag-specific CD4 T cell repertoire.

T-Lymphocyte Subsets - immunology

Sepsis - immunology

T-Lymphocyte Subsets - cytology

CD4-Positive T-Lymphocytes - cytology

Mice, Inbred C57BL

Thymus Gland - cytology

Adoptive Transfer

CD4-Positive T-Lymphocytes - immunology

Animals

Flow Cytometry

Bacterial Infections - immunology

Precursor Cells, T-Lymphoid - cytology

Thymus Gland - immunology

Mice

Precursor Cells, T-Lymphoid - immunology

Disease Models, Animal

Details

Title: Subtitle: Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge
Creators: Javier Cabrera-Perez - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School, Minneapolis, MN 55455; Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455
Stephanie A Condotta - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Britnie R James - Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455
Sakeen W Kashem - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School, Minneapolis, MN 55455; Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455
Erik L Brincks - Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455
Deepa Rai - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Tamara A Kucaba - Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455
Vladimir P Badovinac - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Thomas S Griffith - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School, Minneapolis, MN 55455; Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455; Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455; and Minneapolis VA Health Care System, Minneapolis, MN 55417 tgriffit@umn.edu
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.194(4), pp.1609-1620
DOI: 10.4049/jimmunol.1401711
PMID: 25595784
PMCID: PMC4412277
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI83286 / NIAID NIH HHS I01 BX001324 / BLRD VA R01 AI114543 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS 2T32AI007313 / NIAID NIH HHS P30 CA077598 / NCI NIH HHS R01 GM113961 / NIGMS NIH HHS AI114543 / NIAID NIH HHS
Language: English
Date published: 02/15/2015
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047778002771

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