IL-12 is both required and sufficient for initiating T cell reactivity to a class I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic cells.

  • Bianchi R
  • Grohmann U
  • Belladonna M
  • et al.
67Citations
Citations of this article
20Readers
Mendeley users who have this article in their library.

Abstract

Delayed-type hypersensitivity responses, mediated by CD8+ cells and detected by skin test assay, occur in sensitized mice in response to challenge with a class I-restricted synthetic peptide related to a poorly immunogenic tumor rejection Ag, P815AB, of murine mastocytoma cells. Efficient priming for this response, which requires functional CD4+ cells and production of IFN-gamma in the host, is achieved by transfer of dendritic cells (DC) pulsed in vitro with a physical mixture of P815AB and T helper peptides, such as a class II-restricted synthetic peptide of tetanus toxin. We now show that the adjuvant effect of the T helper peptide was associated with the appearance of early and late IL-12 transcripts in the spleens of DC recipient mice, correlated with a late IFN-gamma response, and was negated by serologic ablation of endogenous IL-12 at the time of cell transfer. rIL-12, administered in vivo to the DC recipient mice, could substitute for the T helper peptide in initiating skin test reactivity following transfer of DC pulsed with P815AB alone, leading to Ag-specific production of IFN-gamma by CD4+ and CD8+ T cells. In vitro and in vivo cell depletion experiments suggested the following: 1) the exogenous IL-12 required both CD4+ and CD8+ cells for activity; 2) the immune response initiated by IL-12 relied on later production of IL-12 by the host; and 3) the early adjuvanticity of the exogenous IL-12 involved improved recognition of class II-restricted epitopes of this otherwise poorly immunogenic tumor peptide.

Cite

CITATION STYLE

APA

Bianchi, R., Grohmann, U., Belladonna, M. L., Silla, S., Fallarino, F., Ayroldi, E., … Puccetti, P. (1996). IL-12 is both required and sufficient for initiating T cell reactivity to a class I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic cells. The Journal of Immunology, 157(4), 1589–1597. https://doi.org/10.4049/jimmunol.157.4.1589

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free