Author:
Jeon Youngwoo,Lim Jung-Yeon,Im Keon-Il,Kim Nayoun,Cho Seok-Goo
Abstract
IntroductionB-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in acute GVHD.MethodsWe examined the effects of belimumab, a monoclonal antibody targeting BAFF, for the treatment of acute GVHD. We examined the effects of T cells and B cells separately when inducing GVHD in mouse model.ResultsTherapeutic functional manipulation of endogenous BAFF can improve acute GVHD during the early post-transplant period. In this study, BAFF was shown to increase the proportions of CD4+IL-17+, CD4+IL-6+ Th17, and CD4+IFN-γ+ Th1 cells and to reduce the proportion of regulatory T (Treg) cells. Furthermore, the belimumab therapy group showed increased B220+IgD+IgM+ mature B cells but decreased B220+IgD−IgM− memory B cells, B220+Fas+GL-7+ germinal center formation, and B220+IgD−CD138+ plasma cells. These results indicate that BAFF can alleviate acute GVHD by simultaneously regulating T and B cells. Interestingly, the BAFF level was higher in patients with acute GVHD after HSCT compared with patients receiving chemotherapy.ConclusionThis study suggests that BAFF blockade might modulate CD4 +T-cell-induced acute GVHD early after allo-HSCT and the possibility of simultaneously controlling chronic GVHD, which may appear later after allo-HSCT.
Subject
Immunology,Immunology and Allergy
Reference31 articles.
1. B-cell stage and context-dependent requirements for survival signals from BAFF and the b-cell receptor;Mackay;Immunol Rev,2010
2. Altered b-cell homeostasis and excess BAFF in human chronic graft-versus-host disease;Sarantopoulos;Blood,2009
3. Bimolecular complex between rolling and firm adhesion receptors required for cell arrest; CD44 association with VLA-4 in T cell extravasation;Nandi;Immunity,2004
4. Bone marrow transplantation in the rat. i. histologic correlations and quantitation of cellular infiltrates in acute graft-versus-host disease;Renkonen;Am J Pathol,1984
5. Bone marrow transplantation in the rat. III. structure of the liver inflammatory lesion in acute graft-versus-host disease;Leszczynski;Am J Pathol,1985
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