Mice deficient in PKC theta demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseases

Autoimmunity. 2006 Sep;39(6):469-78. doi: 10.1080/08916930600907954.


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.

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • Cell Proliferation
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Enzyme Activation
  • Female
  • Inflammation / immunology*
  • Inflammation / pathology
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Isoenzymes / genetics*
  • Isoenzymes / immunology
  • Leukocyte Common Antigens / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • NF-kappa B / metabolism
  • Protein Kinase C / genetics*
  • Protein Kinase C / immunology
  • Protein Kinase C-theta
  • RNA, Messenger / blood
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • Spleen / metabolism


  • CD4 Antigens
  • Cytokines
  • Isoenzymes
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Leukocyte Common Antigens