Mice deficient in PKC theta demonstrate impairedin vivoT cell activation and protection from T cell-mediated inflammatory diseases
| Autor: | Dominic Picarella, Marion Dorsch, Bruce Jaffee, Lisa Schopf, Michael Fitzgerald, Nancy Paz, Tao Wang, Aileen Healy, Michelle Dupont, Karen Anderson, Tim Ocain, Yajun Xu |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Encephalomyelitis Autoimmune Experimental medicine.medical_treatment T cell Immunology Receptors Antigen T-Cell Mice SCID Biology Lymphocyte Activation Mice Immune system Internal medicine medicine Animals Immunology and Allergy RNA Messenger Protein Kinase C Protein kinase C Cell Proliferation Inflammation Mice Knockout Cell growth T-cell receptor NF-kappa B T lymphocyte Inflammatory Bowel Diseases Enzyme Activation Isoenzymes Disease Models Animal Endocrinology Cytokine medicine.anatomical_structure Spinal Cord Protein Kinase C-theta CD4 Antigens Cytokines Leukocyte Common Antigens Female Tumor necrosis factor alpha Lymph Nodes Spleen |
| Zdroj: | Autoimmunity. 39:469-478 |
| ISSN: | 1607-842X 0891-6934 |
| Popis: | In the present study we have characterized T cell-driven immune function in mice that are genetically deficient in PKC theta. In response to simple immunologic stimulation invoked by in vivo T cell receptor (TCR) cross-linking, these mice showed significantly depressed plasma cytokine levels for IL-2, IL-4, IFNgamma, and TNFalpha compared to wild-type (WT) mice. In parallel, spleen mRNA levels for these cytokines were reduced, and NF-kappaB activation was also reduced in PKC theta knockouts (KO). Injection of allogeneic cells into the footpad of PKC theta deficient mice provoked a significantly diminished local T cell response compared to WT mice similarly challenged. Unlike comparable cells from wild type mice, CD45RBhi T cells harvested from PKC theta deficient mice failed to induce colitis in the SCID-CD45RB cell transfer model of IBD. In another T cell-dependent model of inflammatory disease, PKC theta deficient animals developed far less severe neurologic signs and reduced spinal cord inflammatory cell infiltrate compared to WT controls in the MOG-induced EAE model. A fundamental role for PKC theta in T cell activation and in the development of T cell-mediated inflammatory diseases is indicated by these results. |
| Databáze: | OpenAIRE |
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