IL-12/23 Signals Delivered by Dendritic Cells Predominantly Within the First 48 Hours of T cell Priming Dictates the Functional Capacity of CTLs (95.14)

• Published in: The Journal of immunology (1950) 2007-04, Vol.178 (1_Supplement), p.S179-S179
• Main Authors: Henry, Curtis J., Grayson, Jason M., Westcott, Marlena M., Brzoza, Kristina L., Hiltbold, Elizabeth M.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.Supp.95.14

Interleukin-12 is critical in establishing CTL-mediated protective immunity against various pathogens. Our initial studies focusing on the role of IL-12 in dictating CTL function used anti-IL-12p40 antibodies, which neutralize both IL-12 (p35/p40 subunits) and IL-23 (p19/p40 subunits). By monitoring interferon gamma (IFN-γ) production as a measure of CTL differentiation, we determined that IL-12p40 signals were required predominantly during the first 48 hours of priming. However, with these studies we could not assess the individual contributions of IL-12 and IL-23. Therefore, our goal was to evaluate the individual contributions of IL-12 and IL-23 in regulating CTL primary and secondary responses. Wild-type, IL-12p35−/−, or IL-12p40−/− DCs infected with Listeria monocytogenes were used to prime CTLs; IFN-γ and granzyme B were used as measures of CTL differentiation. CTLs primed by IL-12p35 and p40−/− DCs exhibited reduced IFN-γ production; the greatest reduction occurred in CTLs primed by IL-12p40−/− DCs, indicating that IL-23 played a minor role in CTL priming. In addition, mice immunized with IL-12p35−/− DCs exhibited a reduced ability to clear Listeria. This deficiency correlated with fewer CTLs producing IFN-γ upon secondary antigenic exposure. Thus, the magnitude of primary and secondary CTL responses is influenced more by the activity of IL-12 than IL-23 during priming. (NIH AI057770)