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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1609-1620
Number of pages12
JournalJournal of Immunology
Volume194
Issue number4
DOIs
StatePublished - Feb 15 2015

Bibliographical note

Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.

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