Abstract
Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematologic malignancies. However graft-versus-host disease (GVHD) is a major limiting factor for a successful patient outcome. GVHD is a result of alloimmune responses of donor T lymphocytes attacking the recipient's cells and tissues. Chemokine receptor CCR5 plays a role in solid organ allograft rejection and mediates murine GVHD pathogenesis. Herein, we report that infiltrating lymphocytes in the skin of human acute GVHD (aGVHD) samples are predominantly CCR5+ T cells. In addition, we characterized the features of the CCR5 expression on alloreactive T lymphocytes. We found that the CCR5+ population exhibits the characteristics of the activated effector T cell phenotype. CCR5 expression is upregulated upon allogenic stimulation, and CCR5+ cells are proliferating with coexpression of T cell activation markers. Furthermore, the activated T cells producing inflammatory cytokine tumor necrosis factor (TNF)α, interleukin (IL)-2, or interferon (IFN)-γ, are positive for CCR5. Thus, CCR5 is a marker for GVHD effector cells and CCR5+ T cells are active participants in the pathogenesis of human aGVHD.
Original language | English (US) |
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Pages (from-to) | 311-319 |
Number of pages | 9 |
Journal | Biology of Blood and Marrow Transplantation |
Volume | 16 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2010 |
Keywords
- CCR5
- CD4
- CD8
- Chemokine
- GVHD
ASJC Scopus subject areas
- Hematology
- Transplantation