IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells

Clin Immunol. Feb-Mar 2006;118(2-3):159-69. doi: 10.1016/j.clim.2005.09.008. Epub 2005 Nov 3.

Abstract

Memory T cells in human non-small cell lung cancer are unresponsive to progressing tumors. T cells were evaluated at the single cell level by imaging the nuclear translocation of NF-kappaB and NFAT via immunofluorescence confocal microscopy as an early measure of responsiveness to T cell receptor triggering. Little translocation of NF-kappaB or NFAT occurred in tumor-associated T cells in response to CD3+CD28 cross-linking under conditions which led to maximal translocation in normal donor peripheral blood T cells. TNF-alpha induced maximal NF-kappaB translocation in these T cells, indicating that they remain receptive to alternative signaling pathways, and pulsing with IL-12 prior to TCR triggering reversed their apparent anergy. T cells from additional chronic inflammatory microenvironments demonstrated a similar refractoriness to TCR activation, suggesting either that a common regulatory mechanism present within the microenvironment controls these cells or that with continuous antigen exposure, they remain refractory to activation via the TCR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Separation
  • Clonal Anergy / immunology*
  • Humans
  • Immunologic Memory*
  • Interleukin-12 / physiology*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Microscopy, Confocal
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / immunology
  • Signal Transduction / physiology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Receptors, Antigen, T-Cell
  • Tumor Necrosis Factor-alpha
  • Interleukin-12