The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation
| Autor: | Shin-ichiro Fujii, Anthony J. Bonito, Kang Liu, Caroline Smith, Ralph M. Steinman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
T cell
T-Lymphocytes Immunology Antigen presentation CD40 Ligand chemical and pharmacologic phenomena Biology Major histocompatibility complex Lymphocyte Activation Article 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Antigens CD medicine CD40 Immunology and Allergy Animals CD40 Antigens 030304 developmental biology Mice Knockout 0303 health sciences α-galactosylceramide Immunity Cellular Membrane Glycoproteins maturation Tumor Necrosis Factor-alpha hemic and immune systems T helper cell Dendritic cell NKT Dendritic Cells Acquired immune system Natural killer T cell 3. Good health Cell biology Mice Inbred C57BL medicine.anatomical_structure TNF-α biology.protein B7-1 Antigen Female B7-2 Antigen CD80 Spleen 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied alpha-galactosylceramide. This glycolipid activates innate Valpha14(+) natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40(-/-) and CD40L(-/-) mice did not elicit CD4(+) and CD8(+) T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-alpha up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40(-/-) mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation ("signal one") and costimulation ("signal two") to generate functioning CD4(+) T helper cell 1 and CD8(+) cytolytic T lymphocytes. |
| Databáze: | OpenAIRE |
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