Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis

Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity...

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Veröffentlicht in:The Journal of immunology (1950) 2005-06, Vol.174 (11), p.7141-7146
Hauptverfasser: Heuer, Josef G, Zhang, Tonghai, Zhao, Jingyong, Ding, Chunjin, Cramer, Martin, Justen, Kathy L, Vonderfecht, Steven L, Na, Songqing
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container_end_page 7146
container_issue 11
container_start_page 7141
container_title The Journal of immunology (1950)
container_volume 174
creator Heuer, Josef G
Zhang, Tonghai
Zhao, Jingyong
Ding, Chunjin
Cramer, Martin
Justen, Kathy L
Vonderfecht, Steven L
Na, Songqing
description Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity. In this study, we have used murine cecal ligation and puncture as a model of polymicrobial sepsis to explore the effects of adoptive transfer of Tregs on septic outcome. Adoptive transfer of in vitro-stimulated Tregs in both prevention and therapeutic modes significantly improved survival of cecal ligation and puncture mice. Furthermore, the effect was dependent on both the number of Tregs adoptively transferred and the presence of host T cells. Animals that received stimulated Tregs had significantly increased peritoneal mast cells and peritoneal TNF-alpha production. More importantly, adoptive transfer of in vitro-stimulated Tregs significantly improved bacterial clearance, which resulted in improved survival. Our results suggest a novel role for Tregs in sepsis.
doi_str_mv 10.4049/jimmunol.174.11.7141
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subjects Adoptive Transfer - methods
Animals
Cell Movement - immunology
Cells, Cultured
Dose-Response Relationship, Immunologic
Female
Injections, Intravenous
Ligation
Lymphocyte Activation - immunology
Mast Cells - pathology
Mice
Mice, Inbred BALB C
Mice, Nude
Peritoneum - cytology
Peritoneum - immunology
Peritoneum - microbiology
Punctures
Receptors, Interleukin-2 - biosynthesis
Sepsis - immunology
Sepsis - microbiology
Sepsis - mortality
Sepsis - therapy
Survival Analysis
T-Lymphocytes, Regulatory - metabolism
T-Lymphocytes, Regulatory - microbiology
T-Lymphocytes, Regulatory - transplantation
Tumor Necrosis Factor-alpha - biosynthesis
title Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis
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