Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line

Larry Karnitz, Shari L. Sutor, Toshihiko Torigoe, John C. Reed, Michael P. Bell, David J. McKean, Paul J. Leibson, Robert T. Abraham

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

The growth, differentiation, and functional activities of antigen-stimulated T lymphocytes are regulated by the interaction of the T-cell-derived cytokine, interleukin-2 (IL-2), with the high-affinity IL-2 receptor (IL-2R). IL-2R occupancy initiates a rapid increase in intracellular protein tyrosine phosphorylation, suggesting that a receptor-coupled protein tyrosine kinase (PTK) serves as a proximal signaling element for the IL-2R. Previous studies implicated the src-family kinase, p56lck, as a potential IL-2R-linked signal transducer. In this study, we have characterized a spontaneous variant of the IL-2-dependent cytotoxic T-cell line, CTLL-2, which contains no detectable lck-derived mRNA transcripts, protein, or PTK activity. The p56lck-deficient CTLL-2 cells retained strict dependence on IL-2 for both viability and growth, indicating that p56lck activity was not required for the transduction of IL-2-mediated mitogenic signals. However, the p56lck-deficient cells exhibited a moderate decrease in their rate of IL-2-dependent proliferation. In contrast to this relatively modest proliferative defect, the p56lck-deficient cell line displayed a profound reduction in T-cell antigen receptor-dependent cytolytic effector functions. Both the proliferative and the cytolytic defects observed in the p56lck-deficient cells were completely reversed by transfection of these cells with a wild-type lck expression vector. These results indicate that p56lck expression is not obligatory for IL-2-mediated T-cell growth stimulation; however, this PTK plays a central role in the generation T-cell-mediated cytotoxic responses.

Original languageEnglish (US)
Pages (from-to)4521-4530
Number of pages10
JournalMolecular and cellular biology
Volume12
Issue number10
DOIs
StatePublished - Oct 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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