Ectopic T-bet expression licenses dendritic cells for interleukin (IL)-12-independent priming of Type-1 T cells in vitro1

• Published in: The Journal of immunology (1950) Vol. 183; no. 11; pp. 7250 - 7258
• Main Authors: Lipscomb, Michael W., Chen, Lu, Taylor, Jennifer L., Goldbach, Christina, Watkins, Simon C., Kalinski, Pawel, Butterfield, Lisa H., Wesa, Amy K., Storkus, Walter J.
• Format: Journal Article
• Language: English
• Published: 13-11-2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0901477

T-bet (TBX21) is a transcription factor required for the optimal development of Type-1 immune responses. While initially characterized for its intrinsic role in T cell functional polarization, endogenous T-bet may also be critical to the licensing of Type-1-biasing antigen presenting cells. Here, we investigated whether human dendritic cells (DC) genetically engineered to express high levels of T-bet (i.e. DC.Tbet) promote superior Type-1 T cell responses
in vitro
. We observed that DC.Tbet were selective activators of Type-1 effector T cells developed from the naïve pool of responder cells, while DC.Tbet and control DC promoted Type-1 responses equitably from the memory pool of responder cells. Naïve T cells primed by (SEB or tumor-associated protein-loaded) DC.Tbet exhibited an enhancement in Type-1-, and a concomitant reduction in T
H
2- and Treg-associated phenotype/function. Surprisingly, DC.Tbet were impaired in their production of IL-12 family member cytokines (IL-12p70, IL-23 and IL-27) when compared with control DC, and the capacity of DC.Tbet to preferentially prime Type-1 T cell responses was only minimally inhibited by cytokine (IL-12p70, IL-23, IFN-γ) neutralization or receptor (IL-12Rβ2, IL-27R) blockade during T cell priming. The results of transwell assays suggested the DC.Tbet-mediated effects are predominantly the result of direct DC-T cell contact or their close proximity, thereby implicating a novel, IL-12-independent mechanism by which DC.Tbet promote improved Type-1 functional polarization from naïve T cell responders. Given their superior Type-1 polarizing capacity, DC.Tbet may be suitable for use in vaccines designed to prevent/treat cancer or infectious disease.