期刊
BLOOD
卷 111, 期 5, 页码 2929-2940出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-06-096602
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- NCI NIH HHS [R01 CA107096, P30 CA008748, P20 CA 103694, P01 CA023766, CA 33049, P01 CA033049, CA 023766, P20 CA103694, CA 107096] Funding Source: Medline
- NHLBI NIH HHS [R01 HL069929, R01 HL084815-17, HL 69929, R01 HL084815] Funding Source: Medline
- NIAMS NIH HHS [P30 AR042689-159006, P30 AR042689] Funding Source: Medline
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.
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