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Clin Immunol. 2006 Feb-Mar;118(2-3):159-69. Epub 2005 Nov 3.

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

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Department of Microbiology and Immunology, 138 Farber Hall, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.


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.

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