The roles of IL-12 and IL-23 in CD8+ T cell-mediated immunity against Listeria monocytogenes: Insights from a DC vaccination model.
Listeria monocytogenes infection induces a strong inflammatory response characterized by the production of IL-12 and IFN-gamma and protective immunity against this pathogen is dependent on CD8+ T cells (CTL). Recent studies have suggested that these inflammatory cytokines affect the rate of memory CD8+ T cell generation as well as the number of short-lived effector cells generated. The role of the closely related cytokine, IL-23, in this response has not been examined. We hypothesized that IL-12 and IL-23 produced by dendritic cells collectively enhance the generation and function of memory cells. To test this hypothesis, we employed a DC vaccination approach. Mice lacking IL-12 and IL-23 were vaccinated with wild-type (WT), IL-12(-/-), or IL-12/23(-/-) DC and protection to Lm was monitored. Mice vaccinated with WT and IL-12(-/-) DC were resistant to lethal challenge with Lm. Surprisingly, mice vaccinated with IL-12/23(-/-) DC exhibited significantly reduced protection when challenged. Protection correlated with the relative size of the memory pools generated. In summary, these data indicate that IL-23 can partially compensate for the lack of IL-12 in the generation protective immunity against Lm.
Henry
Curtis J
CJ
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Grayson
Jason M
JM
Brzoza-Lewis
Kristina L
KL
Mitchell
Latoya M
LM
Westcott
Marlena M
MM
Cook
Anne S
AS
Hiltbold
Elizabeth M
EM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D016233:Immunotherapy, Active; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
D053759:Interleukin-23; D018664:Interleukin-12