IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells.
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.
Broderick
Lori
L
Department of Microbiology and Immunology, 138 Farber Hall, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.
Brooks
Stephen P
SP
Takita
Hiroshi
H
Baer
Alan N
AN
Bernstein
Joel M
JM
Bankert
Richard B
RB
D021581:Active Transport, Cell Nucleus / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D017635:Clonal Anergy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12