Activation of human dendritic cells through CD40 cross-linking

Dendritic cells, the professional antigen-presenting cells (APC) involved in T cell priming, express CD40, a molecule which triggering plays a key role in B cell growth and differentiation as well as monocyte activation. Herein we demonstrate that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells. Culturing D-Lc on CD40-ligand (CD40L) transfected L cells allowed D-Lc survival as 50 +/- 15% of seeded cells were recovered after 4 d while only 5% survived over control L cells. CD40 activation induced important morphological changes with a reduction of cytoplasmic content and a remarkable increase of dendrite development as well as an altered phenotype. In particular, CD40 triggering induced maintenance of high levels of major histocompatibility complex class II antigens and upregulation of accessory molecules such as CD58, CD80 (B7-1) and CD86 (B7-2). CD40 engagement also seems to turn on D-Lc maturation as illustrated by upregulation of CD25, a molecule usually expressed on interdigitating dendritic cells of secondary lymphoid organs. Finally, CD40 activated D- Lc secreted a limited set of cytokines (TNF-alpha, IL-8, and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) whereas a similar activation induced elutriated monocytes to secrete IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha, and MIP-1 alpha. As D-Lc activated T cells upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with a fibroblast cell line stably expressing CD40L, mimics physiological interactions between dendritic cells and T cells.

[1]  R. Noelle,et al.  CD40 and its ligand. , 1996, Advances in immunology.

[2]  J. Banchereau,et al.  B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells , 1994, The Journal of experimental medicine.

[3]  J. Banchereau,et al.  B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the release of soluble CD40 , 1994, European journal of immunology.

[4]  L. Lanier,et al.  CD40 preferentially costimulates activation of CD4+ T lymphocytes. , 1994, Journal of immunology.

[5]  A. Aruffo,et al.  In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39 , 1993, The Journal of experimental medicine.

[6]  A. Aruffo,et al.  In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-B cell interactions , 1993, The Journal of experimental medicine.

[7]  O. Stutman,et al.  Immune functions of tumor necrosis factor. I. Tumor necrosis factor induces apoptosis of mouse thymocytes and can also stimulate or inhibit IL-6-induced proliferation depending on the concentration of mitogenic costimulation. , 1993, Journal of immunology.

[8]  K. Kishi,et al.  Induction of human IgE synthesis in B cells by mast cells and basophils , 1993, Nature.

[9]  R. Steinman,et al.  Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium , 1993, Journal of Experimental Medicine.

[10]  W. Fanslow,et al.  CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40 , 1993, The Journal of experimental medicine.

[11]  J. Banchereau,et al.  Human B cell precursors proliferate and express CD23 after CD40 ligation , 1993, The Journal of experimental medicine.

[12]  G. Aversa,et al.  The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation , 1993, The Journal of experimental medicine.

[13]  E. Roldán,et al.  Essential role of tumor necrosis factor‐α in the differentiation of human tonsil in vivo induced B cells capable of spontaneous and high‐rate immunoglobulin secretion , 1993, European journal of immunology.

[14]  C. Hsieh,et al.  Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. , 1993, Science.

[15]  I. Stamenkovic,et al.  Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A. Fischer,et al.  CD40 ligand mutations in X-linked immunodeficiency with hyper-IgM , 1993, Nature.

[17]  L. Notarangelo,et al.  Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM , 1993, Nature.

[18]  J. Bajorath,et al.  The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome , 1993, Cell.

[19]  J. Banchereau,et al.  GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells , 1992, Nature.

[20]  P. Cruz,et al.  Cytokine expression by epidermal cell subpopulations. , 1992, The Journal of investigative dermatology.

[21]  H. Spits,et al.  CD40 is functionally expressed on human thymic epithelial cells. , 1992, Journal of immunology.

[22]  J. Abrams,et al.  Strategies of Anti‐Cytokine Monoclonal Antibody Development: Immunoassay of IL‐10 and IL‐5 in Clinical Samples , 1992, Immunological reviews.

[23]  L. Notarangelo,et al.  Immunodeficiency with hyper-IgM (HIM). , 1992, Immunodeficiency reviews.

[24]  A. Aruffo,et al.  CD40 and its ligand, an essential ligand-receptor pair for thymus-dependent B-cell activation. , 1992, Immunology today.

[25]  J. Banchereau,et al.  Potentiation of early hematopoiesis by tumor necrosis factor-alpha is followed by inhibition of granulopoietic differentiation and proliferation. , 1991, Blood.

[26]  J. Banchereau,et al.  Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen , 1991, The Journal of experimental medicine.

[27]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.

[28]  R. Geha,et al.  CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells , 1990, The Journal of experimental medicine.

[29]  J. Larrick,et al.  Cytotoxic mechanism of tumor necrosis factor‐α , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[30]  R. Steinman,et al.  Migration and maturation of Langerhans cells in skin transplants and explants , 1990, The Journal of experimental medicine.

[31]  R. Steinman,et al.  Use of the fluorescence activated cell sorter to enrich dendritic cells from mouse spleen. , 1990, Journal of immunological methods.

[32]  R. Steinman,et al.  The distinct surface of human blood dendritic cells, as observed after an improved isolation method. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Banchereau,et al.  mAb 104, a new monoclonal antibody, recognizes the B7 antigen that is expressed on activated B cells and HTLV-1-transformed T cells. , 1990, Immunology.

[34]  P. Peters,et al.  Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. , 1990, The Journal of investigative dermatology.

[35]  O. Majdic,et al.  Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. , 1989, The Journal of investigative dermatology.

[36]  J. Banchereau,et al.  Activation of human B lymphocytes through CD40 and interleukin 4 , 1989, European journal of immunology.

[37]  I. Stamenkovic,et al.  A B‐lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. , 1989, The EMBO journal.

[38]  E. Clark,et al.  Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. , 1986, Proceedings of the National Academy of Sciences of the United States of America.