Host-reactive CD8+ memory stem cells in graft-versus-host disease.
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.
Zhang
Yi
Y
Department of Medicine, University of Pennsylvania School of Medicine, Room 510, Maloney, 3600 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Joe
Gerard
G
Hexner
Elizabeth
E
Zhu
Jiang
J
Emerson
Stephen G
SG
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D018960:Hyaluronan Receptors / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D000950:Antigens, Ly; D017931:DNA Primers; D018960:Hyaluronan Receptors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D019041:L-Selectin