PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes
| Autor: | Hicham Bouabe, Verity Q. Pearce, Valentina Carbonaro, Amy R. MacQueen, Klaus Okkenhaug |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Infectious Disease and Host Response
Class I Phosphatidylinositol 3-Kinases Immunosenescence T cell Immunology Mice Transgenic Biology CD8-Positive T-Lymphocytes Granzymes Interleukin 21 Interferon-gamma Mice Phosphatidylinositol 3-Kinases Immune system medicine Immunology and Allergy Cytotoxic T cell Animals Listeriosis Phosphorylation Antigen-presenting cell Phosphoinositide-3 Kinase Inhibitors Innate immune system Adoptive Transfer Listeria monocytogenes Cell biology Mice Inbred C57BL medicine.anatomical_structure Cytokines Immunologic Memory Proto-Oncogene Proteins c-akt CD8 Intracellular |
| Zdroj: | The Journal of Immunology Author Choice |
| ISSN: | 1550-6606 |
| Popis: | PI3Ks regulate diverse immune cell functions by transmitting intracellular signals from Ag, costimulatory receptors, and cytokine receptors to control cell division, differentiation, survival, and migration. In this study, we report the effect of inhibiting the p110δ subunit of PI3Kδ on CD8+ T cell responses to infection with the intracellular bacteria Listeria monocytogenes. A strong dependency on PI3Kδ for IFN-γ production by CD8+ T cells in vitro was not recapitulated after Listeria infection in vivo. Inactivation of PI3Kδ resulted in enhanced bacterial elimination by the innate immune system. However, the magnitudes of the primary and secondary CD8+ T cell responses were reduced. Moreover, PI3Kδ activity was required for CD8+ T cells to provide help to other responding CD8+ cells. These findings identify PI3Kδ as a key regulator of CD8+ T cell responses that integrates extrinsic cues, including those from other responding cells, to determine the collective behavior of CD8+ T cell populations responding to infection. |
| Databáze: | OpenAIRE |
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