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

作者：Matthew J. Delano, Philip O. Scumpia, Jason S. Weinstein, Dominique P. Coco, Srinivas Nagaraj, Kindra M. Kelly‐Scumpia, Kerri A. O’Malley, James Lawrence Wynn, S. V. Antonenko, Samer Z. Al‐Quran, Ryan Z. Swan, Chun‐Shiang Chung, Mark A. Atkinson, Reuben Ramphal, Dmitry I. Gabrilovich, Wesley H. Reeves, Alfred Ayala, Joseph Phillips, Drake LaFace, Paul G. Heyworth, Michael J Clare-Salzler, Lyle L. Moldawer · 发表于：The Journal of Experimental Medicine · 年份：2007 · DOI：10.1084/jem.20062602 · 被引用次数：652 · 研究领域：Immune Response and Inflammation、Sepsis Diagnosis and Treatment、Inflammation biomarkers and pathways

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) gamma 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-beta, or the IFN-alpha/beta receptor, is required for complete GR-1(+)CD11b(+) expansion. GR-1(+)CD11b(+) cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization.