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. 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.
Heuer
Josef G
JG
Biotechnology Discovery Research, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Zhang
Tonghai
T
Zhao
Jingyong
J
Ding
Chunjin
C
Cramer
Martin
M
Justen
Kathy L
KL
Vonderfecht
Steven L
SL
Na
Songqing
S
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007275:Injections, Intravenous; D008026:Ligation; D008213:Lymphocyte Activation / Q000276:immunology*; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010537:Peritoneum / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D011677:Punctures; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000382:microbiology* / Q000637:transplantation*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha