Protein kinase C-theta critically regulates the proliferation and survival of pathogen-specific T cells in murine listeriosis.

Abstract

Protein kinase C-theta (PKC-theta) is essential for the activation of T cells in autoimmune disorders, but not in viral infections. To study the role of PKC-theta in bacterial infections, PKC-theta(-/-) and wild-type mice were infected with Listeria monocytogenes (LM). In primary and secondary listeriosis, the numbers of LM-specific CD8 and CD4 T cells were drastically reduced in PKC-theta(-/-) mice, resulting in increased CFUs in spleen and liver of both PKC-theta(-/-) C57BL/6 and BALB/c mice. Furthermore, immunization with peptide-loaded wild-type dendritic cells induced LM-specific CD4 and CD8 T cells in wild-type but not in PKC-theta(-/-) mice. In listeriosis, transfer of wild-type T cells into PKC-theta(-/-) mice resulted in a normal control of Listeria, and, additionally, a selective expression of PKC-theta in LM-specific T cells was sufficient to drive a normal proliferation and survival of these T cells in LM-infected PKC-theta(-/-) recipients, illustrating a cell-autonomous function of PKC-theta in LM-specific T cells. Conversely, adoptively transferred PKC-theta(-/-) T cells were partially rescued from cell death and proliferated in LM-infected wild-type recipients, demonstrating that a PKC-theta deficiency of LM-specific T cells can be partially compensated for by a wild-type environment. Additionally, in vitro experiments showed that only the addition of IL-2, but not an inhibition of caspase-3, induced proliferation and prevented death of PKC-theta(-/-) T cells stimulated with LM-infected wild-type dendritic cells, further demonstrating that the impaired proliferation and survival of PKC-theta(-/-) T cells in listeriosis is not intrinsically fixed and can be experimentally improved.

• Authors: Monika Sakowicz-Burkiewicz, Gopala Nishanth, Ulrike Helmuth, Katrin Drögemüller, Dirk H Busch, Olaf Utermöhlen, Michael Naumann, Martina Deckert, Dirk Schlüter
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 8 Pg. 5601-12 (Apr 15 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18390745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caspase Inhibitors
• Interleukin-2
• Isoenzymes
• Recombinant Fusion Proteins
• Interferon-gamma
• Prkcq protein, mouse
• Protein Kinase C
• Protein Kinase C-theta
• Caspase 3

Topics

• Adoptive Transfer
• Animals
• Arenaviridae Infections (enzymology, immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Caspase 3 (metabolism)
• Caspase Inhibitors
• Cell Proliferation
• Female
• Interferon-gamma (immunology, metabolism)
• Interleukin-2 (immunology, metabolism)
• Isoenzymes (metabolism)
• Listeria monocytogenes (immunology)
• Listeriosis (enzymology, immunology, microbiology)
• Lymphocyte Activation
• Lymphocyte Count
• Lymphocytic choriomeningitis virus (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Protein Kinase C (metabolism)
• Protein Kinase C-theta
• Recombinant Fusion Proteins (immunology, metabolism)