Aberrant germinal center formation, follicular T-helper cells, and germinal center B-cells were involved in chronic graft-versus-host disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-05-12

AUTHORS

Liang Shao, Albert K. W. Lie, You Zhang, Cheuk-Hong Wong, Yok-Lam Kwong

ABSTRACT

Chronic graft-versus-host disease (cGVHD) is an important complication after allogeneic hematopoietic stem cell transplantation (HSCT). To define the roles of T-cells and B-cells in cGVHD, a murine minor histocompatibility complex–mismatched HSCT model was used. Depletion of donor splenocyte CD4+ T-cells and B220+ B-cells alleviated cGVHD. Allogeneic recipients had significantly increased splenic germinal centers (GCs), with significant increases in follicular T-helper (Tfh) cells and GC B-cells. There were increased expressions in Tfh cells of inducible T-cell co-stimulator (ICOS), interleukin (IL)-4 and IL-17, and in GC B-cells of B-cell activating factor receptor and ICOS ligand. Depletion of donor splenocyte CD4+ T-cells abrogated aberrant GC formation and suppressed Tfh cells and GC B-cells. Interestingly, depletion of donor splenocyte B200+ B-cells also suppressed Tfh cells in addition to GC B-cells. These results suggested that in cGVHD, both Tfh and GC B-cells were involved, and their developments were mutually dependent. The mammalian target of rapamycin (mTOR) inhibitor everolimus was effective in suppressing cGVHD, Tfh cells, and GC B-cells, either as a prophylaxis or when cGVHD had established. These results implied that therapeutic targeting of both T-cells and B-cells in cGVHD might be effective. Signaling via mTOR may be another useful target in cGVHD. More... »

PAGES

1493-1504

References to SciGraph publications

  • 2013-05-17. The good, the bad and the ugly — TFH cells in human health and disease in NATURE REVIEWS IMMUNOLOGY
  • 2012-11-23. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis in ARTHRITIS RESEARCH & THERAPY
  • 2012-05-11. Advances in graft-versus-host disease biology and therapy in NATURE REVIEWS IMMUNOLOGY
  • 2013-01-18. Innate B cell helpers reveal novel types of antibody responses in NATURE IMMUNOLOGY
  • 2013-02-11. Human T Follicular Helper Cells: Development and Subsets in CROSSROADS BETWEEN INNATE AND ADAPTIVE IMMUNITY IV
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    http://scigraph.springernature.com/pub.10.1007/s00277-015-2394-z

    DOI

    http://dx.doi.org/10.1007/s00277-015-2394-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023172170

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25963280


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