J Immunol. 2013 Jan 28. [Epub ahead of print]
IL-2 Produced by CD8+ Immune T Cells Can Augment Their IFN-γ Production Independently from Their Proliferation in the Secondary Response to an Intracellular Pathogen
Sa Q, Woodward J, Suzuki Y.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536.
Chronic infection with Toxoplasma gondii induces a potent resistance against reinfection, and IFN-γ production by CD8(+) T cells is crucial for the protective immunity. However, the molecular mechanisms that regulate the secondary response remain to be elucidated. In the current study, we examined the role of IL-2 in IFN-γ production by CD8(+) immune T cells in their secondary responses using T. gondii-specific CD8(+) T cell hybridomas and splenic CD8(+) immune T cells from chronically infected mice. The majority (92%) of CD8(+) T cell hybridomas produced large amounts of IFN-γ only when a low amount (0.5 ng/ml) of exogenous IL-2 was provided in combination with T. gondii Ags. Inhibition of cell proliferation by mitomycin C did not affect the enhancing effect of IL-2 on the IFN-γ production, and significant increases in transcription factor T-bet expression were associated with the IL-2-mediated IFN-γ amplification. Splenic CD8(+) immune T cells produced similar low levels of IL-2 in the secondary response to T. gondii, and a blocking of IL-2 signaling by anti-IL-2Rα Ab or inhibitors of JAK1 and JAK3 significantly reduced IFN-γ production of the T cells. This IL-2-mediated upregulation of IFN-γ production was observed in mitomycin C-treated CD8(+) immune T cells, thus independent from their cell division. Therefore, endogenous IL-2 produced by CD8(+) immune T cells can play an important autocrine-enhancing role on their IFN-γ production in the secondary responses to T. gondii, suggesting an importance of induction of CD8(+) immune T cells with an appropriate IL-2 production for vaccine development.
PMID: 23359502 [PubMed - as supplied by publisher]