In vitro induction of T cell anergy by blocking B7 and early T cell costimulatory molecule ETC-1/B7-2

Immunity. 1994 May;1(2):147-54. doi: 10.1016/1074-7613(94)90108-2.

Abstract

APC-associated B7 and ETC-1/B7-2 are two major costimulatory molecules for full activation of T lymphocytes during auto- and allogeneic immune responses. In this report, we further examine the role of the two molecules in murine CD4+ T cell activation and anergy development. As suggested in antibody blocking studies, optimal activation of CD4+ T cells in response to anti-CD3 stimulation requires collaborative signaling through the two molecules. Simultaneous blockade of B7 and ETC-1/B7-2 renders CD4+ T cells unresponsive to anti-CD3 restimulation. PCR analysis and cytokine reconstitution studies show that the observed unresponsiveness is correlated to a significant reduction of Th1-type cytokine production, suggesting B7 and ETC-1/B7-2-mediated costimulatory signaling may be specifically active in regulation of the function of the Th1 subset.

MeSH terms

  • Animals
  • Antigens, CD*
  • B-Lymphocytes / immunology
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • Binding, Competitive
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / genetics
  • Female
  • Gene Expression
  • Immune Tolerance*
  • In Vitro Techniques
  • Interferon-gamma / pharmacology
  • Interleukin-12 / pharmacology
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Recombinant Proteins
  • Signal Transduction

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Cytokines
  • Interleukin-2
  • Membrane Glycoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-12
  • Interferon-gamma