Role of B7 costimulatory molecules in the adjuvant activity of the heat-labile enterotoxin of Escherichia coli.

Academic Article

Abstract

  • Much interest has been directed at understanding the adjuvant properties of the heat-labile enterotoxin of Escherichia coli (LT). In this study, we have assessed how LT compared with the nonenzymatic mutant LT (E112K) affect the level of B7-1 and B7-2 expression on APCs, and we determined how these costimulatory molecules influence their adjuvant properties. Analysis of B7-1 and B7-2 expression on B cells revealed that LT enhanced B7-2 but not B7-1, while LT (E112K) had no effect on the expression of either costimulatory molecule. Treatment of macrophage or dendritic cells with LT resulted in a predominant enhancement of B7-2, while LT (E112K) induced mainly B7-1 expression. Analysis of LT- and LT (E112K)-treated B cells, macrophage, and dendritic cells also revealed significant differences in their ability to enhance anti-CD3-stimulated CD4(+) T cell proliferative responses via B7-1 and B7-2. Furthermore, the ability of LT to enhance both Ab and CD4(+) T cell responses to a coadministered Ag was severely abrogated in B7-2- but not B7-1-deficient mice. In contrast, the in vivo adjuvant properties of LT (E112K) appeared to be mediated by both B7-1 and B7-2 for optimal CD4(+) T cell responses, while B7-1 appeared to be the predominant B7 molecule involved in the ability of LT (E112K) to augment Ab responses to a coadministered Ag. These findings demonstrate distinct differences in the ability of LT and LT (E112K) to enhance B7-1 and B7-2 on APC, as well as a dependence upon these costimulatory molecules for their adjuvant properties.
  • Keywords

  • Adjuvants, Immunologic, Animals, Antigen-Presenting Cells, Antigens, CD, B-Lymphocytes, B7-1 Antigen, B7-2 Antigen, Bacterial Toxins, CD4-Positive T-Lymphocytes, Enterotoxins, Escherichia coli, Escherichia coli Proteins, Integrin alphaXbeta2, Leukocyte Common Antigens, Lymphocyte Activation, Macrophage-1 Antigen, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Knockout, Point Mutation, Up-Regulation
  • Digital Object Identifier (doi)

    Pubmed Id

  • 2394780
  • Author List

  • Martin M; Sharpe A; Clements JD; Michalek SM
  • Start Page

  • 1744
  • End Page

  • 1752
  • Volume

  • 169
  • Issue

  • 4