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T memory stem cells after allogeneic haematopoietic cell transplantation: unique long-term kinetics and influence of chronic graft-versus-host disease
Authors:Koji Jimbo  Takaaki Konuma  Eri Watanabe  Chisato Kohara  Motoko Mizukami  Etsuko Nagai  Maki Oiwa-Monna  Mai Mizusawa  Masamichi Isobe  Seiko Kato  Satoshi Takahashi  Arinobu Tojo
Affiliation:1. Department of Haematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

K.J. and T.K. contributed equally to this work.;2. Department of Haematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;3. Department of IMSUT Clinical Flow Cytometry Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;4. Department of Laboratory Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Abstract:T memory stem cells (TSCMs) are a subset of primitive T cells capable of both self-renewal and differentiation into all subsets of memory and effector T cells. Therefore, TSCMs may play a role in immune reconstitution and graft-versus-host disease (GVHD) in patients receiving allogeneic haematopoietic cell transplantation (HCT). We conducted a cross-sectional study to evaluate the proportions, absolute counts, phenotypes and functions of TSCMs in 152 adult patients without disease recurrence at least 12 months after undergoing HCT. CD4+ TSCMs were negatively correlated with number of months after transplantation in HCT patients that received cord blood transplantation, but not in patients that received bone marrow transplantation or peripheral blood stem cell transplantation. The proportions and absolute counts of CD4+ TSCMs and expression levels of inducible co-stimulator (ICOS) in CD8+ TSCMs were significantly higher in patients with mild and moderate/severe cGVHD compared to patients without cGVHD. These data suggested that, more than 12 months after allogeneic HCT, the kinetics of CD4+ TSCMs were dependent on the type of donor source, and further that CD4+ TSCMs and ICOS levels in CD8+ TSCMs were associated with cGVHD.
Keywords:T memory stem cells  T cells  immune reconstitution  chronic graft-versus-host disease  cord blood transplantation  allogeneic haematopoietic cell transplantation
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