Immobilized anti-CD3 mAb induces anergy in murine naive and memory CD4+ T cells in vitro

Int Immunol. 1997 Jul;9(7):935-44. doi: 10.1093/intimm/9.7.935.

Abstract

The induction of non-responsiveness in resting murine CD4+ T cells was investigated using immobilized anti-CD3 mAb. Incubation of freshly isolated CD4+ T cells with immobilized anti-CD3 mAb led to apoptosis in 40-60% cells. The surviving cells were profoundly non-responsive to subsequent mitogenic stimulation. The non-responsive state was characterized by a lack of IL-2 production and hyper-responsiveness to added IL-2, but was not explained by further activation-induced cell death. The induction of non-responsiveness was not due to modulation of the TCR-CD3 complex, and required partial activation of the T cells in that it was accompanied by an increase in cell size and was inhibited by addition of cyclosporin A. Finally, analysis of anti-CD3-mediated responses in naive and memory CD4+ T cells, separated on the basis of CD44 expression, showed that both naive and memory T cells have similar sensitivity to immobilized anti-CD3 mAb-induced activation, apoptosis and anergy. These results demonstrate that TCR-CD3 engagement on freshly isolated resting CD4+ naive and memory T cells, In the absence of co-stimulation, as achieved by plastic-immobilized anti-CD3 mAb, induces both anergy and cell death.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / immunology
  • CD3 Complex / immunology*
  • CD3 Complex / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Death / immunology
  • Cells, Cultured
  • Clonal Anergy
  • Female
  • Immunologic Memory / immunology*
  • Interphase / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred CBA

Substances

  • Antibodies, Monoclonal
  • CD3 Complex