Understanding the dendritic cell lineage through a study of cytokine receptors
| Autor: | L L Gill, Gerold Schuler, F Koch, Andreas O. Eggert, C Heufler, Nikolaus Romani, S K Dower, Eckhart Kämpgen, S Gillis |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
T-Lymphocytes
Immunology Antigen presentation Receptors Antigen T-Cell Immunoglobulins Biology Cell Line Mice Skin Physiological Phenomena Animals Immunology and Allergy Receptors Cytokine Antigen-presenting cell Skin Mice Inbred BALB C Mice Inbred C3H Binding Sites Genes Immunoglobulin Follicular dendritic cells Macrophage Colony-Stimulating Factor Granulocyte-Macrophage Colony-Stimulating Factor Articles DNA Dendritic Cells Dendritic cell Recombinant Proteins Up-Regulation Cell biology DC-SIGN Blotting Southern Organ Specificity Receptors Granulocyte-Macrophage Colony-Stimulating Factor Interleukin 15 Interleukin 12 biology.protein Cytokines CC chemokine receptors Spleen Interleukin-1 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function. |
| Databáze: | OpenAIRE |
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