Enterotoxin adjuvants have direct effects on T cells and antigen-presenting cells that result in either interleukin-4-dependent or -independent immune responses

J Infect Dis. 2000 Jul;182(1):180-90. doi: 10.1086/315694. Epub 2000 Jun 30.

Abstract

In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to directly affect activated CD4(+) T cells and support interleukin (IL)-5 production in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. These effects were not influenced by CD40-CD40 ligand cosignaling. Addition of LT- or CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted in the induction of T cell proliferative responses. Further, these responses were inhibited by anti-B7-2 monoclonal antibody. Cocultivation of CD4(+) T cells with LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4-mediated Th2-type cytokine production. The results from in vitro studies were supported by in vivo studies in IL-4(-/-) mice, in which LT induced mucosal IgA responses but CT did not. Thus, although both LT and CT induce mucosal adjuvant responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4-independent Th2-type responses.

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, CD / biosynthesis
  • B7-2 Antigen
  • Bacterial Toxins / immunology*
  • Enterotoxins / immunology*
  • Escherichia coli Proteins*
  • Immunity, Mucosal
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / immunology*
  • Interleukin-5 / biosynthesis
  • Interleukin-6 / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens, CD
  • B7-2 Antigen
  • Bacterial Toxins
  • Cd86 protein, mouse
  • Enterotoxins
  • Escherichia coli Proteins
  • Interleukin-2
  • Interleukin-5
  • Interleukin-6
  • Membrane Glycoproteins
  • heat-labile enterotoxin, E coli
  • stN protein, Vibrio cholerae
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma