Co-immunisation with DNA encoding RANK/RANKL or 4-1BBL costimulatory molecules does not enhance effector or memory CTL responses afforded by immunisation with a tumour antigen-encoding DNA vaccine

  • Herd K
  • Wiethe C
  • Tindle R
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Abstract

T cell mediated immune responses are induced following interaction of MHC-presented epitope on professional antigen presenting cells such as dendritic cells (DCs) with cognate T cell receptor. Up-regulation of receptor-ligand pairs of costimulatory molecules linking DC to T cell enhances the resulting T cell responses. This 'second signalling' occurs through the B7 molecules CD80/86 expressed by DCs, and importantly through members of the TNF ligand/TNF receptor superfamilies. We have previously shown that co-expression of RANK/RANKL or 41BB-L in addition to tumour antigen in dendritic cells augmented cognate effector and memory tumour antigen-directed cytotoxic T cell responses when the DCs were used to immunise mice. Here, we examined whether co-immunisation with naked plasmid DNAs encoding antigen and these costimulatory molecule(s), would enhance antigen specific T cell responses. We demonstrate that co-immunisation with DNAs encoding tumour antigen and costimulatory molecules failed to enhance antigen-directed CTL responses, or tumour protection, afforded by immunisation with DNA encoding tumour antigen alone. © 2007 Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • Costimulation
  • DNA vaccine
  • T cell response

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Authors

  • Karen A. Herd

  • Carsten Wiethe

  • Robert W. Tindle

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