Dendritic cell-derived IL-12 is not required for the generation of cytotoxic, IFN-gamma-secreting, CD8(+) CTL in vivo.
By using adoptive transfer of Ag-loaded bone marrow-derived dendritic cells (BMDC), we have established an in vivo model of CTL priming. Activation of CTL in these experiments required both CD4(+) T cells and CD154, demonstrating that this model reflects CD4(+) T cell-dependent dendritic cell (DC) licensing. Because IL-12 has been suggested to play an important role in CTL activation by DC, we examined the ability of BMDC to prime CTL in the complete absence of IL-12 using p40-deficient mice. We observed that the absence of IL-12 does not affect the phenotype or allostimulatory function of BMDC after in vitro maturation. Moreover, there was no difference in the ability of Ag-loaded DC to elicit CTL cytotoxicity, whether the Ag was delivered by virus infection or peptide pulsing. Equal frequencies of Ag-specific, IFN-gamma-secreting CD8(+) T cells developed in both wild-type and IL-12-deficient backgrounds. Finally, CTL generated in the IL-12-deficient environment were capable of protecting immunized mice against tumor challenge, demonstrating that these CTL were fully functional, despite the absence of IL-12 during the maturation process in vivo. These results indicate that IL-12 is not critical for the development of IFN-gamma secreting, CD8(+) T cells and that another mechanism must be used by licensed DC to prime and activate CTL.
Wan
Y
Y
Center for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. wanyong@mcmaster.ca
Lu
L
L
Bramson
J L
JL
Baral
S
S
Zhu
Q
Q
Pilon
A
A
Dayball
K
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis*; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D016827:CD8 Antigens; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin