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Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease

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  • Ruishu Deng

    (Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope
    Hematologic Malignancies and Stem Cell Transplantation Institute, The Beckman Research Institute of City of Hope
    Discovery Institute)

  • Christian Hurtz

    (University of California
    Division of Hematology and Oncology, University of Pennsylvania)

  • Qingxiao Song

    (Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope
    Hematologic Malignancies and Stem Cell Transplantation Institute, The Beckman Research Institute of City of Hope
    Fujian Institute of Hematology, Fujian Medical University Union Hospital)

  • Chanyu Yue

    (The Beckman Research Institute of City of Hope)

  • Gang Xiao

    (University of California
    The Beckman Research Institute of City of Hope)

  • Hua Yu

    (The Beckman Research Institute of City of Hope)

  • Xiwei Wu

    (The Beckman Research Institute of City of Hope)

  • Markus Muschen

    (University of California
    The Beckman Research Institute of City of Hope)

  • Stephen Forman

    (Hematologic Malignancies and Stem Cell Transplantation Institute, The Beckman Research Institute of City of Hope)

  • Paul J. Martin

    (Fred Hutchinson Cancer Research Center, University of Washington)

  • Defu Zeng

    (Diabetes and Metabolism Research Institute, The Beckman Research Institute of City of Hope
    Hematologic Malignancies and Stem Cell Transplantation Institute, The Beckman Research Institute of City of Hope)

Abstract

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome mediated by pathogenic CD4+ T and B cells, but the function of extrafollicular and germinal center CD4+ T and B interactions in cGVHD pathogenesis remains largely unknown. Here we show that extrafollicular CD4+ T and B interactions are sufficient for inducing cGVHD, while germinal center formation is dispensable. The pathogenesis of cGVHD is associated with the expansion of extrafollicular CD44hiCD62loPSGL-1loCD4+ (PSGL-1loCD4+) T cells. These cells express high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and ameliorates cGVHD. Expansion of PSGL-1loCD4+ T cells is also prevented by BCL6 or Stat3 deficiency in donor CD4+ T cells, with the induction of cGVHD ameliorated by BCL6 deficiency and completely suppressed by Stat3 deficiency in donor CD4+ T cells. These results support that Stat3- and BCL6-dependent extrafollicular CD4+ T and B interactions play critical functions in the pathogenesis of cGVHD.

Suggested Citation

  • Ruishu Deng & Christian Hurtz & Qingxiao Song & Chanyu Yue & Gang Xiao & Hua Yu & Xiwei Wu & Markus Muschen & Stephen Forman & Paul J. Martin & Defu Zeng, 2017. "Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00880-2
    DOI: 10.1038/s41467-017-00880-2
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