TY - JOUR
T1 - Tolerogenic dendritic cells pulsed with enterobacterial extract suppress development of colitis in the severe combined immunodeficiency transfer model
AU - Pedersen, Anders Elm
AU - Gad, M
AU - Kristensen, N N
AU - Haase, C
AU - Nielsen, C H
AU - Claesson, M H
N1 - Keywords: Adoptive Transfer; Animals; Antigens, Bacterial; CD4-Positive T-Lymphocytes; Cell Proliferation; Colitis; Cytokines; Dendritic Cells; Disease Models, Animal; Enterobacteriaceae; Female; Immune Tolerance; Immunophenotyping; Interleukin-10; Lymphocyte Activation; Lymphocyte Transfusion; Mice; Mice, Inbred BALB C; Mice, SCID
PY - 2007
Y1 - 2007
N2 - Immunomodulatory dendritic cells (DCs) that induce antigen-specific T-cell tolerance upon in vivo adoptive transfer are promising candidates for immunotherapy of autoimmune diseases. The feasibility of such a strategy has recently proved its efficacy in animal models of allotransplantation and experimental allergic encephalitis, but the effect in inflammatory bowel disease has not yet been demonstrated. In severe combined immunodeficient (SCID) mice, adoptively transferred CD4(+) CD25(-) T cells repopulate the lymphoid tissues and lead to development of chronic colitis characterized by CD4(+) T-cell proliferation against enterobacterial extract in vitro. In this model, we adoptively transferred in-vitro-generated bone-marrow-derived DCs exposed to interleukin-10 (IL-10) and an enterobacterial extract. We show that these cells are CD11c positive with intermediate expression of CD40, CD80 and CD86 and have a diminished secretion of IL-6, IL-12 p40/70, tumour necrosis factor-alpha and keratinocyte-derived chemokine (KC) compared to DCs treated with enterobacterial extract alone. In vivo, these cells prevented weight loss in SCID mice adoptively transferred with CD4(+) CD25(-) T cells, resulted in a lower histopathology colitis score and tended to result in higher serum levels of IL-1alpha, IL-10, IL-12, IL-13, IL-17, KC and monokine induced by interferon-gamma (MIG). These data underscore the potential of using immunomodulatory DCs to control inflammatory bowel disease and demonstrate its potential use in future human therapeutic settings.
AB - Immunomodulatory dendritic cells (DCs) that induce antigen-specific T-cell tolerance upon in vivo adoptive transfer are promising candidates for immunotherapy of autoimmune diseases. The feasibility of such a strategy has recently proved its efficacy in animal models of allotransplantation and experimental allergic encephalitis, but the effect in inflammatory bowel disease has not yet been demonstrated. In severe combined immunodeficient (SCID) mice, adoptively transferred CD4(+) CD25(-) T cells repopulate the lymphoid tissues and lead to development of chronic colitis characterized by CD4(+) T-cell proliferation against enterobacterial extract in vitro. In this model, we adoptively transferred in-vitro-generated bone-marrow-derived DCs exposed to interleukin-10 (IL-10) and an enterobacterial extract. We show that these cells are CD11c positive with intermediate expression of CD40, CD80 and CD86 and have a diminished secretion of IL-6, IL-12 p40/70, tumour necrosis factor-alpha and keratinocyte-derived chemokine (KC) compared to DCs treated with enterobacterial extract alone. In vivo, these cells prevented weight loss in SCID mice adoptively transferred with CD4(+) CD25(-) T cells, resulted in a lower histopathology colitis score and tended to result in higher serum levels of IL-1alpha, IL-10, IL-12, IL-13, IL-17, KC and monokine induced by interferon-gamma (MIG). These data underscore the potential of using immunomodulatory DCs to control inflammatory bowel disease and demonstrate its potential use in future human therapeutic settings.
U2 - 10.1111/j.1365-2567.2007.02600.x
DO - 10.1111/j.1365-2567.2007.02600.x
M3 - Journal article
C2 - 17428312
SN - 0953-4954
VL - 121
SP - 526
EP - 532
JO - Immunology. Supplement
JF - Immunology. Supplement
IS - 4
ER -
