Organ-derived dendritic cells have differential effects on alloreactive T cells

被引：26

作者：

Kim, Theo D. ^{[1
]}

Terwey, Theis H. ^{[1
]}

Zakrzewski, Johannes L. ^{[1
]}

Suh, David ^{[1
]}

Kochman, Adam A. ^{[1
]}

Chen, Megan E. ^{[1
]}

King, Chris G. ^{[1
]}

Borsotti, Chiara ^{[1
]}

Grubin, Jeremy ^{[1
]}

Smith, Odette M. ^{[1
]}

Heller, Glenn ^{[2
]}

Liu, Chen ^{[3
,4
]}

Murphy, George F. ^{[5
]}

Alpdogan, Onder ^{[1
]}

van den Brink, Marcel R. M. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Lab Allogene Bone Marrow Transplantat, Dept Med & Immunol, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[3] Univ Florida, Coll Med, Dept Pathol Immunol, Gainesville, FL USA

[4] Univ Florida, Coll Med, Lab Med, Gainesville, FL USA

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

BLOOD | 2008年 / 111卷 / 05期

关键词：

D O I：

10.1182/blood-2007-06-096602

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2929 / 2940

页数：12