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.
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.
Department of Microbiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Qila
Q
Sa
Jerold
J
Woodward
Yasuhiro
Y
Suzuki
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000494:pharmacology; D013154:Spleen / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D000098815:T-bet Transcription Factor
D000906:Antibodies; D000953:Antigens, Protozoan; D007376:Interleukin-2; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016685:Mitomycin; D007371:Interferon-gamma; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3