title: Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge.
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.
authors.affiliation: 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;
authors.forename: Javier
authors.initials: J
authors.lastname: Cabrera-Perez
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Condotta
authors.affiliation: Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455;
authors.forename: Britnie R
authors.initials: BR
authors.lastname: James
authors.affiliation: 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;
authors.forename: Sakeen W
authors.initials: SW
authors.lastname: Kashem
authors.affiliation: Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455;
authors.forename: Erik L
authors.initials: EL
authors.lastname: Brincks
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
authors.forename: Deepa
authors.initials: D
authors.lastname: Rai
authors.affiliation: Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455;
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Kucaba
authors.affiliation: 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;
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
authors.affiliation: 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.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology