Impaired cytolytic activity in peripheral blood T cells from renal cell carcinoma patients

Classic T lymphocyte cytotoxicity is mediated through the T cell receptor (TCR). Defects in TCR signal transduction and cytolytic activity have been reported in tumor infiltrating T lymphocytes. We hypothesized that impaired cytotoxicity occurs in peripheral blood T cells from renal cell carcinoma (...

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Bibliographic Details
Published in:Clinical Immunology 2005-10, Vol.117 (1), p.6-11
Main Authors: Crocenzi, Todd S., Tretter, Christopher P.G., Schwaab, Thomas, Schned, Alan R., Heaney, John A., Cole, Bernard F., Fisher, Jan L., Ernstoff, Marc S.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Carcinoma, Renal Cell - immunology
CD3 Complex - immunology
CD3 Complex - metabolism
CD8 Antigens - immunology
CD8 Antigens - metabolism
Cytolytic T lymphocytes
Cytotoxicity, Immunologic
Female
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunopathology
Interleukin-2 - immunology
Kidney Neoplasms - immunology
Lymphocyte Activation - immunology
Male
Medical sciences
Middle Aged
Receptors, Antigen, T-Cell - immunology
Recombinant Proteins - immunology
Redirected cytotoxicity
Renal cell carcinoma
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
TCR signal transduction
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Summary:Classic T lymphocyte cytotoxicity is mediated through the T cell receptor (TCR). Defects in TCR signal transduction and cytolytic activity have been reported in tumor infiltrating T lymphocytes. We hypothesized that impaired cytotoxicity occurs in peripheral blood T cells from renal cell carcinoma (RCC) that can be reversed by exposure to rhIL-2. Peripheral blood mononuclear cells (PBMC) from 29 RCC patients and 29 healthy volunteers were isolated and cultured in the absence or presence of 10 IU/ml rhIL-2. A redirected cytotoxicity assay that requires TCR signal transduction was used with chromium-labeled P815 target cells, effector PBMC and anti-CD3 antibody. Target cell lysis was measured in “lytic units” (LU). Mean LU from RCC patients was lower than that of healthy volunteers (105.8 LU vs. 194.6 LU, P = 0.025). Exposure to rhIL-2 increased T cell-mediated lysis in both groups. Disruption of T cell cytotoxicity in RCC patients can be overcome by exposure to rhIL-2.
ISSN:1521-6616
1521-7035
1365-2567
DOI:10.1016/j.clim.2005.06.010