Organ-derived dendritic cells have differential effects on alloreactive T cells.
Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target organs liver and spleen or skin- and gut-draining lymph nodes effectively primed naive allogeneic T cells in vitro with the exception of liver-derived dendritic cells, which showed less stimulatory capacity. Gut-derived dendritic cells induced alloreactive donor T cells with a gut-homing phenotype that caused increased GVHD mortality and morbidity compared with T cells stimulated with dendritic cells from spleen, liver, and peripheral lymph nodes in an MHC-mismatched murine BMT model. However, in vivo analysis demonstrated that the in vitro imprinting of homing molecules on alloreactive T cells was only transient. In conclusion, organ-derived dendritic cells can efficiently induce specific homing molecules on alloreactive T cells. A gut-homing phenotype correlates with increased GVHD mortality and morbidity after murine BMT, underlining the importance of the gut in the pathophysiology of GVHD.
Kim
Theo D
TD
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Terwey
Theis H
TH
Zakrzewski
Johannes L
JL
Suh
David
D
Kochman
Adam A
AA
Chen
Megan E
ME
King
Chris G
CG
Borsotti
Chiara
C
Grubin
Jeremy
J
Smith
Odette M
OM
Heller
Glenn
G
Liu
Chen
C
Murphy
George F
GF
Alpdogan
Onder
O
van den Brink
Marcel R M
MR
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000187:drug effects; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D016023:Integrins; D007519:Isoantigens; D008024:Ligands; D008070:Lipopolysaccharides; D016201:Receptors, Lymphocyte Homing; D019087:Selectins; C071777:integrin alpha4beta7