MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis

Matthew J. Delano, Philip O. Scumpia, Jason Weinstein, Dominique Coco, Srinivas Nagaraj, Kindra M. Kelly-Scumpia, Kerri A. O'Malley, James L. Wynn, Svetlana Antonenko, Samer Z. Al-Quran, Ryan Swan, Chun Shiang Chung, Mark A. Atkinson, Reuben Ramphal, Dmitry I. Gabrilovich, Wesley H. Reeves, Alfred Ayala, Joseph Phillips, Drake LaFace, Paul G. HeyworthMichael Clare-Salzler, Lyle L. Moldawer

Research output: Contribution to journalArticle

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Abstract

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1 +CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b + expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. JEM

Original languageEnglish (US)
Pages (from-to)1463-1474
Number of pages12
JournalJournal of Experimental Medicine
Volume204
Issue number6
DOIs
StatePublished - Jun 11 2007

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Sepsis
T-Lymphocytes
Interferons
Population
Interferon Receptors
CD8 Antigens
Th2 Cells
Th1 Cells
Toll-Like Receptor 4
Adaptive Immunity
Chemokines
Interleukin-10
Antibody Formation
Spleen
Lymph Nodes
Bone Marrow
Cell Proliferation
Cytokines
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Delano, Matthew J. ; Scumpia, Philip O. ; Weinstein, Jason ; Coco, Dominique ; Nagaraj, Srinivas ; Kelly-Scumpia, Kindra M. ; O'Malley, Kerri A. ; Wynn, James L. ; Antonenko, Svetlana ; Al-Quran, Samer Z. ; Swan, Ryan ; Chung, Chun Shiang ; Atkinson, Mark A. ; Ramphal, Reuben ; Gabrilovich, Dmitry I. ; Reeves, Wesley H. ; Ayala, Alfred ; Phillips, Joseph ; LaFace, Drake ; Heyworth, Paul G. ; Clare-Salzler, Michael ; Moldawer, Lyle L. / MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 6. pp. 1463-1474.
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abstract = "Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1 +CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b + expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. JEM",
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Delano, MJ, Scumpia, PO, Weinstein, J, Coco, D, Nagaraj, S, Kelly-Scumpia, KM, O'Malley, KA, Wynn, JL, Antonenko, S, Al-Quran, SZ, Swan, R, Chung, CS, Atkinson, MA, Ramphal, R, Gabrilovich, DI, Reeves, WH, Ayala, A, Phillips, J, LaFace, D, Heyworth, PG, Clare-Salzler, M & Moldawer, LL 2007, 'MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis', Journal of Experimental Medicine, vol. 204, no. 6, pp. 1463-1474. https://doi.org/10.1084/jem.20062602

MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis. / Delano, Matthew J.; Scumpia, Philip O.; Weinstein, Jason; Coco, Dominique; Nagaraj, Srinivas; Kelly-Scumpia, Kindra M.; O'Malley, Kerri A.; Wynn, James L.; Antonenko, Svetlana; Al-Quran, Samer Z.; Swan, Ryan; Chung, Chun Shiang; Atkinson, Mark A.; Ramphal, Reuben; Gabrilovich, Dmitry I.; Reeves, Wesley H.; Ayala, Alfred; Phillips, Joseph; LaFace, Drake; Heyworth, Paul G.; Clare-Salzler, Michael; Moldawer, Lyle L.

In: Journal of Experimental Medicine, Vol. 204, No. 6, 11.06.2007, p. 1463-1474.

Research output: Contribution to journalArticle

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T1 - MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis

AU - Delano, Matthew J.

AU - Scumpia, Philip O.

AU - Weinstein, Jason

AU - Coco, Dominique

AU - Nagaraj, Srinivas

AU - Kelly-Scumpia, Kindra M.

AU - O'Malley, Kerri A.

AU - Wynn, James L.

AU - Antonenko, Svetlana

AU - Al-Quran, Samer Z.

AU - Swan, Ryan

AU - Chung, Chun Shiang

AU - Atkinson, Mark A.

AU - Ramphal, Reuben

AU - Gabrilovich, Dmitry I.

AU - Reeves, Wesley H.

AU - Ayala, Alfred

AU - Phillips, Joseph

AU - LaFace, Drake

AU - Heyworth, Paul G.

AU - Clare-Salzler, Michael

AU - Moldawer, Lyle L.

PY - 2007/6/11

Y1 - 2007/6/11

N2 - Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1 +CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b + expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. JEM

AB - Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1 +CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b + expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. JEM

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