Differential effects of B7-1 and B7-2 on the costimulation of mouse nonspecific cytotoxic T lymphocyte development in response to anti-CD3 antibody

J Leukoc Biol. 1999 Nov;66(5):792-802. doi: 10.1002/jlb.66.5.792.

Abstract

Despite extensive study, the relative contribution of B7-1 and B7-2 molecules to the costimulation of cytotoxic T lymphocyte (CTL) activation remains controversial. We used blocking mAbs to B7-1 and B7-2 molecules to determine the role of these B7 family members in the in vitro induction of mouse nonspecific CTL in response to soluble anti-CD3 mAb. Optimal induction of anti-CD3-activated killer-T (AK-T) cells was found to require interactions with B7-2 on residual accessory cells in nylon wool-nonadherent spleen cell preparations during the first 12 h of culture in the presence of anti-CD3 mAb. Because B7-1 is not expressed at high enough levels on residual accessory cells in primary T cell cultures to be an effective ligand for CD28, we used LPS-stimulated B cells, which express substantial B7-1, in addition to B7-2, to determine the contribution of B7-1 to AK-T cell development. Compared with B7-2, the contribution of B7-1 to the costimulation of AK-T cells in this system was modest because anti-B7-1 mAb had only a minimal inhibitory effect on the generation of cytotoxicity, whereas anti-B7-2 mAb strongly inhibited AK-T cell development. Anti-CD3-induced cytotoxicity of T cells from CD4 knockout mice and CD4-depleted nylon wool-nonadherent spleen cells from wild-type mice was inhibited by anti-B7-2 mAb, implying that B7-2 is able to bind directly to CD28 on CD8+ T cells and costimulate their activation. B7-1 blockade, on the other hand, did not affect the costimulation of CD8+ T cells. Blockade of B7-2/ CD28 interactions with anti-B7-2 mAb strongly inhibited granzyme B, but not perforin or Fas ligand gene expression, suggesting an explanation for the inhibitory effect of anti-B7-2 mAb on AK-T cell development. These data indicate that B7-2 is superior to B7-1 as a costimulator of mouse AK-T cell induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • CD28 Antigens / biosynthesis
  • CD28 Antigens / immunology
  • CD3 Complex / immunology*
  • CD3 Complex / physiology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Female
  • Granzymes
  • Killer Cells, Natural / immunology
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogens / pharmacology
  • Serine Endopeptidases / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD3 Complex
  • Cd86 protein, mouse
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Mitogens
  • Granzymes
  • Gzmb protein, mouse
  • Serine Endopeptidases