title: Aberrant germinal center formation, follicular T-helper cells, and germinal center B-cells were involved in chronic graft-versus-host disease.
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.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shao
authors.forename: Albert K W
authors.initials: AK
authors.lastname: Lie
authors.forename: You
authors.initials: Y
authors.lastname: Zhang
authors.forename: Cheuk-Hong
authors.initials: CH
authors.lastname: Wong
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000276:immunology
chemical_list: C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D020381:Interleukin-17; D015847:Interleukin-4; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases