Multiple paths for activation of naive CD8+ T cells: CD4-independent help

J Immunol. 2001 Aug 1;167(3):1283-9. doi: 10.4049/jimmunol.167.3.1283.

Abstract

CD8(+) CTLs play a pivotal role in immune responses against many viruses and tumors. Two models have been proposed. The "three-cell" model focuses on the role of CD4(+) T cells, proposing that help is only provided to CTLs by CD4(+) T cells that recognize Ag on the same APC. The sequential "two-cell" model proposes that CD4(+) T cells can first interact with APCs, which in turn activate naive CTLs. Although these models provide a general framework for the role of CD4(+) T cells in mediating help for CTLs, a number of issues are unresolved. We have investigated the induction of CTL responses using dendritic cells (DCs) to immunize mice against defined peptide Ags. We find that help is required for activation of naive CTLs when DCs are used as APCs, regardless of the origin or MHC class I restriction of the peptides we studied in this system. However, CD8(+) T cells can provide self-help if they are present at a sufficiently high precursor frequency. The important variable is the total number of T cells responding, because class II-knockout DCs pulsed with two noncompeting peptides are effective in priming.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Communication / genetics
  • Cell Communication / immunology
  • Cells, Cultured
  • Cytotoxicity, Immunologic / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Glycoproteins / immunology
  • Histocompatibility Antigens Class II / biosynthesis
  • Interphase / genetics
  • Interphase / immunology
  • Lymphocyte Activation* / genetics
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Peptide Fragments / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Viral Proteins / immunology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus