Loss of protein kinase C theta, Bcl10, or Malt1 selectively impairs proliferation and NF-kappa B activation in the CD4+ T cell subset

J Immunol. 2008 Nov 1;181(9):6244-54. doi: 10.4049/jimmunol.181.9.6244.


The cytosolic proteins protein kinase Ctheta (PKCtheta), Bcl10, and Malt1 play critical roles in TCR signaling to the transcription factor NF-kappaB. Our data confirm that CD4(+) T cells from PKCtheta, Bcl10, and Malt1 knockout mice show severe impairment of proliferation in response to TCR stimulation. Unexpectedly, we find that knockout CD8(+) T cells proliferate to a similar extent as wild-type cells in response to strong TCR signals, although a survival defect prevents their accumulation. Both CD4(+) and CD8(+) knockout T cells express activation markers, including CD25, following TCR stimulation. Addition of exogenous IL-2 rescues survival of knockout CD4(+) and CD8(+) T cells, but fails to overcome the proliferation defect of CD4(+) T cells. CD4(+) T cells from knockout mice are extremely deficient in TCR-induced NF-kappaB activation, whereas NF-kappaB activation is only partially impaired in CD8(+) T cells. Overall, our results suggest that defects in TCR signaling through PKCtheta, Bcl10, and Malt1 predominantly impair NF-kappaB activation and downstream functional responses of CD4(+) T cells. In contrast, CD8(+) T cells maintain substantial NF-kappaB signaling, implying the existence of a significant TCR-regulated NF-kappaB activation pathway in CD8(+) T cells that is independent of PKCtheta, Bcl10, and Malt1.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology
  • Amino Acid Sequence
  • Animals
  • B-Cell CLL-Lymphoma 10 Protein
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Caspases / deficiency*
  • Caspases / genetics
  • Caspases / physiology
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics
  • Isoenzymes / physiology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitomycin / immunology
  • Molecular Sequence Data
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neoplasm Proteins / deficiency*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Ovalbumin / immunology
  • Protein Kinase C / deficiency*
  • Protein Kinase C / genetics
  • Protein Kinase C / physiology
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / genetics
  • Signal Transduction / immunology


  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • Isoenzymes
  • Ligands
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Mitomycin
  • Ovalbumin
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Caspases
  • Malt1 protein, mouse
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein