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

• Published in: Blood Vol. 111; no. 5; pp. 2929 - 2940
• Main Authors: Kim, Theo D., Terwey, Theis H., Zakrzewski, Johannes L., Suh, David, Kochman, Adam A., Chen, Megan E., King, Chris G., Borsotti, Chiara, Grubin, Jeremy, Smith, Odette M., Heller, Glenn, Liu, Chen, Murphy, George F., Alpdogan, Onder, van den Brink, Marcel R.M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.03.2008; The Americain Society of Hematology; American Society of Hematology
• Series: Transplantation
• Subjects: Animals; Biological and medical sciences; Cell Proliferation - drug effects; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Gene Expression Profiling; Graft vs Host Disease; Hematologic and hematopoietic diseases; Humans; Integrins - metabolism; Isoantigens - immunology; Ligands; Lipopolysaccharides - pharmacology; Liver - cytology; Liver - drug effects; Lymphocyte Activation - drug effects; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Organ Specificity - drug effects; Phenotype; Receptors, Lymphocyte Homing - genetics; Receptors, Lymphocyte Homing - metabolism; Selectins - metabolism; Survival Rate; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transplantation; Up-Regulation - drug effects; Up-Regulation - genetics; Isoimmunization; Dendritic cell; Hematology; Antigen presenting cell; T-Lymphocyte; Organ
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-06-096602

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.