Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase

Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in fully mature as well as immature CD123+ DCs. IDO+ DCs could also be readily detected in vivo, which suggests that these cells may represent a regulatory subset of APCs in humans.

[1]  D. Keskin,et al.  Cells Expressing Indoleamine 2,3-Dioxygenase Inhibit T Cell Responses1 , 2002, The Journal of Immunology.

[2]  P. Robbins,et al.  Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. , 2002, Diabetes.

[3]  Michel C. Nussenzweig,et al.  Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  W. Heath,et al.  Immunity or tolerance? That is the question for dendritic cells , 2001, Nature Immunology.

[5]  C. Uyttenhove,et al.  IL-6 Inhibits the Tolerogenic Function of CD8α+ Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase1 , 2001, The Journal of Immunology.

[6]  A. Cochran,et al.  Sentinel Lymph Nodes Show Profound Downregulation of Antigen-Presenting Cells of the Paracortex: Implications for Tumor Biology and Treatment , 2001, Modern Pathology.

[7]  C. Chambers.  The expanding world of co-stimulation: the two-signal model revisited. , 2001, Trends in immunology.

[8]  U. Grohmann,et al.  CD40 Ligation Ablates the Tolerogenic Potential of Lymphoid Dendritic Cells1 , 2001, The Journal of Immunology.

[9]  Milton W. Taylor,et al.  Indoleamine 2,3-Dioxygenase Production by Human Dendritic Cells Results in the Inhibition of T Cell Proliferation , 2000, The Journal of Immunology.

[10]  D. Munn,et al.  Inhibition of  T Cell Proliferation by Macrophage Tryptophan Catabolism , 1999, The Journal of experimental medicine.

[11]  J. Orenstein,et al.  The macrophage origin of the HIV-expressing multinucleated giant cells in hyperplastic tonsils and adenoids. , 1999, Ultrastructural pathology.

[12]  D. Munn,et al.  Prevention of allogeneic fetal rejection by tryptophan catabolism. , 1998, Science.

[13]  A. Enk,et al.  Induction of tolerance by IL-10-treated dendritic cells. , 1997, Journal of immunology.

[14]  D. Niederwieser,et al.  Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. , 1996, Journal of immunological methods.

[15]  D. Munn,et al.  Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. A potential mechanism of antigen-specific peripheral lymphocyte deletion. , 1996, Journal of immunology.

[16]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[17]  D. Keskin,et al.  Functional expression of indoleamine 2,3-dioxygenase by murine CD8α+ dendritic cells , 2002 .