ovalbumin and curdlan

Induction of cellular immunity is important for effective cancer immunotherapy. Although various antigen carriers for cancer immunotherapy have been developed to date, balancing efficient antigen delivery to antigen presenting cells (APCs) and their activation

Topics: Animals; Antigen-Presenting Cells; beta-Glucans; Biocompatible Materials; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cytokines; Female; Hydrogen-Ion Concentration; Immunity, Cellular; Immunotherapy; Liposomes; Macrophage Activation; Mice; Mice, Inbred C57BL; Neoplasms; Ovalbumin; Tumor Microenvironment

Epicutaneous sensitization with protein allergen that induces predominant Th2 responses is an important sensitization route in atopic dermatitis. Fungal components have been shown to modulate Th cell differentiation. However, the effects of fungal components on epicutaneous sensitization are unclear.. In this study, we showed that co-administration of curdlan, a dectin-1 agonist, during epicutaneous ovalbumin sensitization of BALB/c mice decreased the IL-5 and IL-13 levels in supernatants of lymph node cell ovalbumin reactivation cultures. Mechanistically, curdlan co-administration decreased IL-4 and IL-1β expressions in draining lymph nodes. Curdlan co-administration also lower the migration of langerin+ CD103- epidermal Langerhans cells into draining lymph nodes at 96 hours post-sensitization which might be attributed to decreased expressions of IL-18 and IL-1β in patched skin. Moreover, adoptive transfer of CFSE-labeled transgenic CD4 T cells confirmed that curdlan co-administration decreased the proliferation and IL-4-production of ovalbumin -specific T cells primed by epidermal Langerhans cells.. These results indicated that concurrent exposure to a dectin-1 agonist suppresses the epicutaneously induced Th2 response by modulating the cytokine expression profiles in draining LNs and the migration of epidermal Langerhans cells. These results highlight the effects of fungal components on epicutaneous allergen sensitization in atopic diseases.

Topics: Administration, Cutaneous; Allergens; Animals; Antigens, Surface; beta-Glucans; CD4-Positive T-Lymphocytes; Cell Movement; Dermatitis, Atopic; Interleukin-13; Interleukin-5; Lectins, C-Type; Lymph Nodes; Mannose-Binding Lectins; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

We have examined the potential to generate bona fide macrophages (MØ) from conditionally immortalised murine bone marrow precursors. MØ can be derived from Hoxb8 conditionally immortalised macrophage precursor cell lines (MØP) using either M-CSF or GM-CSF. When differentiated in GM-CSF (GM-MØP) the resultant cells resemble GM-CSF bone marrow-derived dendritic cells (BMDC) in morphological phenotype, antigen phenotype and functional responses to microbial stimuli. In spite of this high similarity between the two cell types and the ability of GM-MØP to effectively present antigen to a T-cell hybridoma, these cells are comparatively poor at priming the expansion of IFN-γ responses from naïve CD4(+) T cells. The generation of MØP from transgenic or genetically aberrant mice provides an excellent opportunity to study the inflammatory role of GM-MØP, and reduces the need for mouse colonies in many studies. Hence differentiation of conditionally immortalised MØPs in GM-CSF represents a unique in vitro model of inflammatory monocyte-like cells, with important differences from bone marrow-derived dendritic cells, which will facilitate functional studies relating to the many 'sub-phenotypes' of inflammatory monocytes.

Topics: Animals; Antigen Presentation; Antigens, Surface; beta-Glucans; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Transformed; Cytokines; Dendritic Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Homeodomain Proteins; Interferon-gamma; Interleukin-2; Lectins, C-Type; Lipopeptides; Lipopolysaccharides; Macrophage Colony-Stimulating Factor; Macrophages; Membrane Proteins; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Monocyte-Macrophage Precursor Cells; Nerve Tissue Proteins; Nitric Oxide; Ovalbumin; Transduction, Genetic; Zymosan

DC NK lectin group receptor-1 (DNGR-1, also known as CLEC9A) is a C-type lectin receptor expressed by mouse CD8alpha+ DC and by their putative equivalents in human. DNGR-1 senses necrosis and regulates CD8+ T-cell cross-priming to dead-cell-associated antigens. In addition, DNGR-1 is a target for selective in vivo delivery of antigens to DC and the induction of CD8+ T-cell and Ab responses. In this study, we evaluated whether DNGR-1 targeting can be additionally used to manipulate antigen-specific CD8+ T lymphocytes. Injection of small amounts of antigen-coupled anti-DNGR-1 mAb into mice promoted MHC class II antigen presentation selectively by CD8alpha+ DC. In the steady state, this was sufficient to induce proliferation of antigen-specific naïve CD4+ T cells and to drive their differentiation into Foxp3+ regulatory lymphocytes. Co-administration of adjuvants prevented this induction of tolerance and promoted immunity. Notably, distinct adjuvants allowed qualitative modulation of CD4+ T-cell behavior: poly I:C induced a strong IL-12-independent Th1 response, whereas curdlan led to the priming of Th17 cells. Thus, antigen targeting to DNGR-1 is a versatile approach for inducing functionally distinct CD4+ T-cell responses. Given the restricted pattern of expression of DNGR-1 across species, this strategy could prove useful for developing immunotherapy protocols in humans.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; Antigen Presentation; beta-Glucans; CD4-Positive T-Lymphocytes; CD8 Antigens; CD8-Positive T-Lymphocytes; Dendritic Cells; Epitopes; Forkhead Transcription Factors; Immune Tolerance; Lectins, C-Type; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ovalbumin; Peptide Fragments; Poly I-C; Receptors, Immunologic; Specific Pathogen-Free Organisms; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th1 Cells