ABSTRACT
BACKGROUND: Influenza A viral infection is concerned with induction of asthma. CD11c+ pulmonary antigen presenting cells (APCs) play a central role in sensitization with inhaled antigens during the acute phase of influenza A viral infection and also reside on bronchial epithelium for the long term after sensitization. To investigate the role of CD11c+ pulmonary APCs in the inhaled antigen sensitization during the acute phase of influenza A viral infection, we analyzed their function. METHODS: Mice were infected with influenza A virus and were sensitized intranasally with BSA/alum during the acute phase of influenza A viral infection. Expression of surface antigens on CD11c+ pulmonary APCs was analyzed by FACS. Cytokine production from CD11c+ pulmonary APCs, and interaction between CD11c+ pulmonary APCs and naïve CD4+ T cells was assessed by ELISA. Ability of antigen presentation by CD11c+ pulmonary APCs was measured by proliferation assay. RESULTS: BSA antigen sensitization during the acute phase of influenza A viral infection induced eosinophil recruitment into the lungs after BSA antigen challenge and moderately increased expression of MHC class II molecules on CD11c+ pulmonary APCs. The interaction between the CD11c+ pulmonary APCs and naïve CD4+ T cells secreted large amounts of IL-10. CONCLUSIONS: BSA antigen sensitization during the acute phase of influenza A viral infection enhanced IL-10 production from naïve CD4+ T cell interaction with CD11c+ pulmonary APCs. The IL-10 secretion evoked Th2 responses in the lungs with downregulation of Th1 responses and was important for the eosinophil recruitment into the lungs after BSA antigen challenge.
Subject(s)
Antigen-Presenting Cells/immunology , Asthma/immunology , CD11c Antigen/immunology , Influenza A Virus, H1N1 Subtype , Influenza, Human/immunology , Serum Albumin, Bovine/immunology , Acute Disease , Animals , Antigens/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Disease Models, Animal , Eosinophils/metabolism , Female , Genes, MHC Class II/immunology , Humans , Immunization , Influenza, Human/complications , Interleukin-10/biosynthesis , Lung/immunology , Mice , Mice, Inbred C57BL , Ovalbumin/immunologyABSTRACT
Alymphoplasia (aly/aly) mice are from a naturally occurring strain with a mutation in nuclear factor-kappa B inducing kinase (NIK). The NIK mutation causes disruption of the architecture of the thymus and spleen and aly/aly mice show decreased numbers of CD25+CD4+T cells in the spleen. For the expansion of CD25+CD4+T cells, interactions between dendritic cells (DCs) and CD25+CD4+ regulatory T cells are necessary. We investigated the ability of DCs to induce expansion of CD25+CD4+T cells. We found that DCs are reduced in the spleen of aly/aly mice, and showed low expressions of CD80, CD86 and MHC class II molecules on the surface. DCs from aly/aly mice showed decreased ability to present ovalbumin (OVA) to T cells from OVA specific TCR transgenic mice, and a decreased ability for alloantigen presentation. Further, DCs showed a decreased ability to induce expansion of CD25+CD4+T cells in vitro. Our results suggested that the impairment of DCs in aly/aly mice is responsible, at least in part, for the decreased numbers of CD25+CD4+T cells in the periphery of aly/aly mice.
Subject(s)
CD4 Antigens/immunology , Dendritic Cells/pathology , Interleukin-2 Receptor alpha Subunit/immunology , Lymphatic Diseases/genetics , T-Lymphocytes, Regulatory/pathology , Animals , Antigen Presentation , B7-1 Antigen/immunology , B7-2 Antigen/immunology , Cell Differentiation , Cells, Cultured , Dendritic Cells/immunology , Genes, MHC Class II , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Ovalbumin/immunology , Spleen/pathology , T-Lymphocytes, Regulatory/immunologyABSTRACT
BACKGROUND: It is well known that cyclophosphamide (Cy) treatment before sensitization paradoxically enhances rather than suppresses contact hypersensitivity (CH) reactions. In fact, Cy-treated mice developed a significant (p < 0.05) increase of the CH reactions to 2,4,6-trinitro-1-chrolobenzene (TNCB) in comparison with untreated mice. OBJECTIVE: In order to examine whether the target cells of Cy in the immuno-augmentative effect are CD25(+) CD4(+) regulatory T cells or not, we investigated effect of Cy treatment on CD25(+) CD4(+) T cells. METHOD: We examined Cy-treated CD25(+) CD4(+) T cells by flow cytometer and by inhibition assay on proliferation of CD25(-) CD4(+) T cells. RESULTS: Cy treatment remarkably reduced the number and percentage of CD25(+) CD4(+) T cells in the spleen and lymph nodes 3 and 5 days later. Moreover, CD25(+) CD4(+) T cells taken from the Cy-treated mice 3 days later showed the lower suppressive activity on proliferation of CD25(-) CD4(+) T cells, as compared to that from the untreated mice. Furthermore, transfer of CD25(+) CD4(+) T cells from untreated mice resulted in a significant decrease (p < 0.05) of the CH reactions enhanced by Cy treatment. CONCLUSION: These results indicate that enhancement of the CH reactions to TNCB by Cy treatment is attributed to the decrease in the number, percentage and the function of CD25(+) CD4(+) regulatory T cells.