Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-a and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-alpha+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-a knockout TNF-alpha-/- (B6;129S-Tnf(tm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-alpha+/+ mice. Injection of anti-TNF-alpha antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-alpha+/+ and Balb/c mice than in the TNF-alpha-/- mice and anti-TNF-alpha or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-a and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-alpha and IgE by anti-TNF-a or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.
Animals ; Dermatitis, Contact/genetics/*immunology/*metabolism/pathology ; Ear/pathology ; Immunoglobulin E/*immunology ; Leukocytes ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Phthalic Anhydrides/*toxicity ; Research Support, Non-U.S. Gov't ; Time Factors ; Tumor Necrosis Factor-alpha/deficiency/genetics/*metabolism

In this study, we investigated the effects of T-cell suppression on the pathogenesis of subgroup J avian leukosis virus (ALV-J). Chickens were treated with cyclosporin A (CSP) 50 mg/Kg body weight or a corresponding volume of olive oil per every three days after hatching until the end of experiment. Some of the chickens from each treatment group were infected with an isolate of ALV-J, ADOL-7501, at 2 weeks of age. The effects of viral infection were compared to uninfected birds in same treatment group. Intramuscular injection of CSP induced significant T-cell specific immunosuppression determined by decreased cutaneous basophilic hypersensitivity response and decreased lymphocyte mitogenic activity using concanavalin A. Most of the chickens examined had Marek's disease virus infection prior to 3 weeks of age. The percentage of antibody-positive birds and antibody titers were similar in infected chickens between both treatment groups. The ratio of viremic chickens was significantly higher in CSP treated group than that of the Oil treated group. Microscopically, one CSP treated chicken had a nephroblastoma at 10 weeks post infection. At 7 and 10 weeks post-infection, more chickens had myeloid cell infiltrations in multiple organs including heart, liver and occasionally lung. Expression of ALV-J viral antigen determined by immunohistochemical staining was significantly higher in CSP treated chickens than Oil treated chickens at 10 weeks post-infection. This study indicated that chemically-induced T-cell suppression may enhance pathogenicity of the AVL-J virus in broilers.
Animals ; Antibodies, Viral/blood ; Avian Leukosis/*immunology/virology ; Avian leukosis virus/genetics/*immunology ; Body Weight ; *Chickens ; Cyclosporine/*pharmacology ; Dermatitis, Contact/immunology/virology ; Flow Cytometry ; Immunocompromised Host ; Immunohistochemistry/veterinary ; Immunophenotyping ; Immunosuppressive Agents/*pharmacology ; Lymphocyte Activation/immunology ; Marek Disease/*immunology/virology ; RNA, Viral/chemistry/genetics ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; T-Lymphocytes/*immunology/virology ; Viremia/veterinary

4-1BB, a transmembrane molecule, member of the tumor necrosis factor receptor superfamily, is an important costimulatory molecule in the immune response, plays a key role in the clonal expansion and survival of CD8(+)T cells. In this study, we investigated 4-1BB regulation of CD4(+)T cell responses using 4-1BB transgenic (TG) mice that constitutively expressed 4-1BB on mature T cells. We first showed that CD4(+)T cells of 4-1BB TG mice had more sustained proliferative capacity in response to TCR/4-1BB stimulation in vitro compared to WT mice. Secondly, 4-1BB TG mice exhibited a more elevated contact hypersensitivity (CHS) response mediated by CD4+ Th1 cells due to more vigorous expansion of and apoptotic inhibition of CD4(+)T cells. Finally, CD4(+)T cells of 4-1BB TG mice had a heightened capacity for T cell priming. Overall, our results demonstrate the involvement of 4-1BB in CD4(+)Th1 cell responses by regulating the clonal expansion and survival of CD4(+)T cells as seen in CD8(+)T cells.
Animals ; Antibodies/immunology ; Antigens, CD ; Antigens, CD137 ; CD4-Positive T-Lymphocytes/cytology/*immunology/*metabolism ; Cell Division ; Cell Lineage ; Dermatitis, Contact/genetics/immunology ; Flow Cytometry ; Gene Expression ; Mice ; Mice, Transgenic ; Receptors, Nerve Growth Factor/*genetics/*metabolism ; Receptors, Tumor Necrosis Factor/*genetics/*metabolism

This study is to elucidate the immunoregulation mechanisms of artesunate (AST) on allergic contact dermatitis (ACD). Pharmacodynamics analyses, HE staining, semi-quantitative RT-PCR and Western blotting were used to explore the effects of AST on the related cytokines, transcription factor and signaling molecule of ACD respectively. The results indicated that topical administration of AST not only reduced the increase of ear swelling, spleen index and inflammatory cells infiltration in ACD mice, but also inhibited remarkably the expression of IFN-gamma, T-bet and NF-kappaB p65. It's suggested that AST could exhibit suppressive effects on inflammatory response and immune function of ACD, which indicates the possibility of developing AST as a novel immunoregulatory agent in the treatment of ACD and other immune-related diseases.
Administration, Topical ; Animals ; Artemisinins ; administration & dosage ; chemistry ; pharmacology ; Dermatitis, Allergic Contact ; immunology ; metabolism ; pathology ; Ear ; pathology ; Female ; GATA3 Transcription Factor ; genetics ; metabolism ; Hypersensitivity, Delayed ; drug therapy ; Immunosuppressive Agents ; administration & dosage ; chemistry ; pharmacology ; Interferon-gamma ; genetics ; metabolism ; Interleukin-4 ; genetics ; metabolism ; Mice ; Mice, Inbred ICR ; Molecular Structure ; NF-kappa B ; metabolism ; RNA, Messenger ; metabolism ; T-Box Domain Proteins ; genetics ; metabolism