1. Mice deficient in PKC theta demonstrate impairedin vivoT cell activation and protection from T cell-mediated inflammatory diseases
- Author
-
Dominic Picarella, Marion Dorsch, Bruce Jaffee, Lisa Schopf, Michael Fitzgerald, Nancy Paz, Tao Wang, Aileen Healy, Michelle Dupont, Karen Anderson, Tim Ocain, and Yajun Xu
- Subjects
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 - Abstract
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.
- Published
- 2006