The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA

J Immunol. 2001 Mar 1;166(5):3061-6. doi: 10.4049/jimmunol.166.5.3061.

Abstract

DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response. In this study, MHC class II(-/-) mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD / physiology*
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / genetics
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • CD4 Antigens / genetics
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism
  • CD40 Antigens / physiology*
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • CD40 Ligand / physiology
  • Cytotoxicity, Immunologic* / genetics
  • DNA, Bacterial / administration & dosage
  • DNA, Bacterial / biosynthesis
  • DNA, Bacterial / immunology
  • Drug Synergism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / physiology*
  • Injections, Intradermal
  • Lymphocyte Activation / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmids / administration & dosage
  • Plasmids / immunology*
  • Plasmids / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / biosynthesis
  • Vaccines, DNA / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD4 Antigens
  • CD40 Antigens
  • Cd86 protein, mouse
  • DNA, Bacterial
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • Vaccines, DNA
  • CD40 Ligand