Role of dendritic cells in the generation of regulatory T cells.

The induction of antigen-specific T-cell tolerance in the thymus and its maintenance in the periphery is crucial for the prevention of autoimmunity. It was recently proposed that cells of the dendritic family not only control immunity but also maintain tolerance to self-antigens, two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. The tolerogenic function of dendritic cells has been shown to be dependent on certain maturation stages and subsets of different ontogenies, and can be influenced by immunomodulatory agents. Here we discuss the current knowledge of these tolerogenic dendritic cells and how might the understanding of the function and characterization of tolerance-inducing dendritic cells be relevant to therapeutic applications.

[1]  R. Steinman,et al.  The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells , 2000, The Journal of experimental medicine.

[2]  Simon C Watkins,et al.  CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: critical role in migration from the tumor site to draining lymph nodes. , 2000, Cancer research.

[3]  A. Pain,et al.  Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells , 1999, Nature.

[4]  F. Koning,et al.  Distribution of HLA class II molecules in epidermal Langerhans cells in situ , 1995, European journal of immunology.

[5]  R. Steinman,et al.  Efficient Presentation of Phagocytosed Cellular Fragments on the Major Histocompatibility Complex Class II Products of Dendritic Cells , 1998, The Journal of experimental medicine.

[6]  Gerold Schuler,et al.  Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? , 2002, Trends in immunology.

[7]  Yong‐jun Liu,et al.  Mouse and human dendritic cell subtypes , 2002, Nature Reviews Immunology.

[8]  M. Udey,et al.  Regulation of expression of B7 by murine Langerhans cells: a direct relationship between B7 mRNA levels and the level of surface expression of B7 by Langerhans cells. , 1993, The Journal of investigative dermatology.

[9]  J. Streilein,et al.  Studies on the induction of anterior chamber‐associated immune deviation (ACAID) III. Induction of ACAID depends upon intraocular transforming growth factor‐β , 1992, European journal of immunology.

[10]  H. Drexhage,et al.  A study of cells present in peripheral lymph of pigs with special reference to a type of cell resembling the langerhans cell , 1979, Cell and Tissue Research.

[11]  A. Khoruts,et al.  Visualizing the generation of memory CD4 T cells in the whole body , 2001, Nature.

[12]  G. Randolph Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. , 2001, Seminars in immunology.

[13]  Hervé Groux,et al.  A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis , 1997, Nature.

[14]  H. von Boehmer,et al.  Anergy and suppression regulate CD4+ T cell responses to a self peptide , 2000, European journal of immunology.

[15]  C. Caux,et al.  Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites , 1998, The Journal of experimental medicine.

[16]  C. Elson,et al.  Bacterial-Reactive T Regulatory Cells Inhibit Pathogenic Immune Responses to the Enteric Flora1 , 2002, The Journal of Immunology.

[17]  R. Coffman,et al.  T Regulatory Cells 1 Inhibit a Th2-Specific Response In Vivo1 , 2000, The Journal of Immunology.

[18]  A. Thomson,et al.  Effects of Liver-Derived Dendritic Cell Progenitors on Th1- and Th2-Like Cytokine Responses In Vitro and In Vivo1 , 2000, The Journal of Immunology.

[19]  R. Schwartz,et al.  A cell culture model for T lymphocyte clonal anergy. , 1990, Science.

[20]  D. Pennington,et al.  CD36 or αvβ3 and αvβ5 Integrins Are Not Essential for MHC Class I Cross-Presentation of Cell-Associated Antigen by CD8α+ Murine Dendritic Cells1 , 2002, The Journal of Immunology.

[21]  P. De Baetselier,et al.  Regulation of Dendritic Cell Numbers and Maturation by Lipopolysaccharide in Vivo , 1996 .

[22]  W. V. Berghe,et al.  N-Acetyl-l-Cysteine Inhibits Primary Human T Cell Responses at the Dendritic Cell Level: Association with NF-κB Inhibition , 1999, The Journal of Immunology.

[23]  Freddie H. Fu,et al.  Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients. , 1996, Transplantation.

[24]  H. Weiner,et al.  Induction and mechanism of action of transforming growth factor‐β‐secreting Th3 regulatory cells , 2001, Immunological reviews.

[25]  S. Sakaguchi,et al.  Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation , 1996, The Journal of experimental medicine.

[26]  Nina Bhardwaj,et al.  Antigen-Specific Inhibition of Effector T Cell Function in Humans after Injection of Immature Dendritic Cells , 2001, The Journal of experimental medicine.

[27]  R. Pauwels,et al.  Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes , 2001, The Journal of experimental medicine.

[28]  Simon C Watkins,et al.  Aspirin Inhibits In Vitro Maturation and In Vivo Immunostimulatory Function of Murine Myeloid Dendritic Cells1 , 2001, The Journal of Immunology.

[29]  D. Hudrisier,et al.  Preferential Recognition of Self Antigens Despite Normal Thymic Deletion of CD4+CD25+ Regulatory T Cells1 , 2002, The Journal of Immunology.

[30]  N. Netzer,et al.  Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant spreading. , 2002, The Journal of clinical investigation.

[31]  D. Umetsu,et al.  Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen , 2001, Nature Immunology.

[32]  H. Groux,et al.  Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. , 2003, Immunity.

[33]  Ethan M. Shevach,et al.  Constitutive Presentation of a Natural Tissue Autoantigen Exclusively by Dendritic Cells in the Draining Lymph Node , 2002, The Journal of experimental medicine.

[34]  Michel C. Nussenzweig,et al.  Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo , 2001, The Journal of experimental medicine.

[35]  Y. Mishima MELANOSOMES IN PHAGOCYTIC VACUOLES IN LANGERHANS CELLS , 1966, The Journal of cell biology.

[36]  C. Pénit,et al.  Regulatory Cd4 T Cells: Expression of Il-2rα Chain, Resistance to Clonal Deletion and Il-2 Dependency , 1998 .

[37]  F. Huang,et al.  A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes , 2000, The Journal of experimental medicine.

[38]  P. Snow,et al.  Induction of Autoantigen-Specific Th2 and Tr1 Regulatory T Cells and Modulation of Autoimmune Diabetes1 , 2003, The Journal of Immunology.

[39]  A. Lanzavecchia,et al.  Inhibition of dendritic cell maturation by herpes simplex virus , 1999, European journal of immunology.

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

[41]  C Caux,et al.  Immunobiology of dendritic cells. , 2000, Annual review of immunology.

[42]  A. Régnault,et al.  TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. , 1999, Journal of immunology.

[43]  A. Hoerauf,et al.  Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). , 2002, Microbes and infection.

[44]  E. Parr,et al.  Langerhans cells phagocytose vaginal epithelial cells undergoing apoptosis during the murine estrous cycle. , 1991, Biology of reproduction.

[45]  P. Allavena,et al.  Glucocorticoids affect human dendritic cell differentiation and maturation. , 1999, Journal of immunology.

[46]  Y. Uehara,et al.  A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph , 1996, The Journal of experimental medicine.

[47]  R. Steinman,et al.  Transport of peptide-MHC class II complexes in developing dendritic cells. , 2000, Science.

[48]  J. Pestka,et al.  Lactobacilli Differentially Modulate Expression of Cytokines and Maturation Surface Markers in Murine Dendritic Cells1 , 2002, The Journal of Immunology.

[49]  Y. Liu,et al.  Dendritic Cell Subsets and Lineages, and Their Functions in Innate and Adaptive Immunity , 2001, Cell.

[50]  S. Grabbe,et al.  Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide , 1993, Nature.

[51]  D. Carbone,et al.  Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. , 1998, Journal of immunology.

[52]  M. Moser,et al.  Effect of interleukin‐10 on dendritic cell maturation and function , 1997, European journal of immunology.

[53]  S. Nishikawa,et al.  Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells. , 2001, International immunology.

[54]  P. Ricciardi-Castagnoli,et al.  Infection of dendritic cells by murine cytomegalovirus induces functional paralysis , 2001, Nature Immunology.

[55]  L. Adorini,et al.  1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation , 2000, The Journal of Immunology.

[56]  T. Blankenstein,et al.  Cross-priming versus cross-tolerance: are two signals enough? , 2002, Trends in immunology.

[57]  C Danieli,et al.  Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products , 1995, The Journal of experimental medicine.

[58]  H. Weiner,et al.  Oral tolerance for the treatment of autoimmune diseases. , 1997, Annual review of medicine.

[59]  H. Link,et al.  Autoantigen‐pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats , 2000, Clinical and experimental immunology.

[60]  P. Koebel,et al.  Anatomical Origin of Dendritic Cells Determines Their Life Span in Peripheral Lymph Nodes , 2000, The Journal of Immunology.

[61]  G. Macpherson,et al.  Dendritic cell heterogeneity in vivo: two functionally different dendritic cell populations in rat intestinal lymph can be distinguished by CD4 expression. , 1998, Journal of immunology.

[62]  P. Allavena,et al.  The chemokine receptor switch paradigm and dendritic cell migration: its significance in tumor tissues , 2000, Immunological reviews.

[63]  P. Allavena,et al.  Vitamin D3 Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells1 , 2000, The Journal of Immunology.

[64]  P. Ricciardi-Castagnoli,et al.  Differential effects of corticosteroids during different stages of dendritic cell maturation , 2000, European journal of immunology.

[65]  M. Toda,et al.  Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. , 1995, Journal of immunology.

[66]  G. Schuler,et al.  Immature dendritic cells generated with low doses of GM‐CSF in the absence of IL‐4 are maturation resistant and prolong allograft survival in vivo , 2000, European journal of immunology.

[67]  N. Yawalkar,et al.  Characterization of human skin-derived CD1a-positive lymph cells , 1999, Archives of Dermatological Research.

[68]  A. Enk,et al.  Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells , 2000, The Journal of experimental medicine.

[69]  H. Weiner,et al.  Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. , 1994, Science.

[70]  B. Dutia,et al.  Characterization of sheep afferent lymph dendritic cells and their role in antigen carriage , 1989, The Journal of experimental medicine.

[71]  R. Matasić,et al.  Cyclooxygenase‐independent inhibition of dendritic cell maturation by aspirin , 2000, Immunology.

[72]  K. Mills,et al.  Pathogen-specific T Regulatory 1 Cells Induced in the Respiratory Tract by a Bacterial Molecule that Stimulates Interleukin 10 Production by Dendritic Cells , 2002, The Journal of experimental medicine.

[73]  H. Waldmann,et al.  Dendritic cells and prospects for transplantation tolerance. , 2000, Current opinion in immunology.

[74]  A. Iwasaki,et al.  Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells , 1999, The Journal of experimental medicine.

[75]  A. Poggi,et al.  The selective engulfment of apoptotic bodies by dendritic cells is mediated by the αvβ3 integrin and requires intracellular and extracellular calcium , 1997 .

[76]  F. Otsuka,et al.  Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. , 1999, Journal of immunology.