Host-reactive CD8+ memory stem cells in graft-versus-host disease

Nat Med. 2005 Dec;11(12):1299-305. doi: 10.1038/nm1326. Epub 2005 Nov 20.


Graft-versus-host disease (GVHD) is caused by alloreactive donor T cells that trigger host tissue injury. GVHD develops over weeks or months, but how this immune response is maintained over time is unknown. In mouse models of human GVHD, we identify a new subset of postmitotic CD44(lo)CD62L(hi)CD8(+) T cells that generate and sustain all allogeneic T-cell subsets in GVHD reactions, including central memory, effector memory and effector CD8(+) T cells, while self-renewing. These cells express Sca-1, CD122 and Bcl-2, and induce GVHD upon transfer into secondary recipients. The postmitotic CD44(lo)CD62L(hi)CD8(+) T cells persist throughout the course of GVHD, are generated in the initial phase in response to alloantigens and dendritic cells and require interleukin-15. Thus, their long life, ability to self-renew and multipotentiality define these cells as candidate memory stem cells. Memory stem cells will be important targets for understanding and influencing diverse chronic immune reactions, including GVHD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Line
  • DNA Primers
  • Flow Cytometry
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hyaluronan Receptors / immunology
  • Immunologic Memory / immunology*
  • L-Selectin / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*


  • Antigens, Ly
  • DNA Primers
  • Hyaluronan Receptors
  • Ly6a protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-2
  • L-Selectin