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

Larry M 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

174 Citations (Scopus)

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
StatePublished - Oct 1992

Fingerprint

Interleukin-2
Interleukin-2 Receptors
T-Lymphocytes
Cell Line
Growth
Protein-Tyrosine Kinases
src-Family Kinases
Receptor Protein-Tyrosine Kinases
T-Cell Antigen Receptor
Transducers
Transfection
Tyrosine
Proteins
Phosphorylation
Cytokines
Antigens
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Karnitz, L. M., Sutor, S. L., Torigoe, T., Reed, J. C., Bell, M. P., McKean, D. J., ... Abraham, R. T. (1992). Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line. Molecular and Cellular Biology, 12(10), 4521-4530.

Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line. / Karnitz, Larry M; Sutor, Shari L.; Torigoe, Toshihiko; Reed, John C.; Bell, Michael P.; McKean, David J.; Leibson, Paul J.; Abraham, Robert T.

In: Molecular and Cellular Biology, Vol. 12, No. 10, 10.1992, p. 4521-4530.

Research output: Contribution to journalArticle

Karnitz, LM, Sutor, SL, Torigoe, T, Reed, JC, Bell, MP, McKean, DJ, Leibson, PJ & Abraham, RT 1992, 'Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line', Molecular and Cellular Biology, vol. 12, no. 10, pp. 4521-4530.
Karnitz, Larry M ; Sutor, Shari L. ; Torigoe, Toshihiko ; Reed, John C. ; Bell, Michael P. ; McKean, David J. ; Leibson, Paul J. ; Abraham, Robert T. / Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line. In: Molecular and Cellular Biology. 1992 ; Vol. 12, No. 10. pp. 4521-4530.
@article{6cf3de2d724f45d69f014561736fb143,
title = "Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line",
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.",
author = "Karnitz, {Larry M} and Sutor, {Shari L.} and Toshihiko Torigoe and Reed, {John C.} and Bell, {Michael P.} and McKean, {David J.} and Leibson, {Paul J.} and Abraham, {Robert T.}",
year = "1992",
month = "10",
language = "English (US)",
volume = "12",
pages = "4521--4530",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Effects of p56lck Deficiency on the Growth and Cytolytic Effector Function of an Interleukin-2-Dependent Cytotoxic T-Cell Line

AU - Karnitz, Larry M

AU - Sutor, Shari L.

AU - Torigoe, Toshihiko

AU - Reed, John C.

AU - Bell, Michael P.

AU - McKean, David J.

AU - Leibson, Paul J.

AU - Abraham, Robert T.

PY - 1992/10

Y1 - 1992/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026611039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026611039&partnerID=8YFLogxK

M3 - Article

C2 - 1406641

AN - SCOPUS:0026611039

VL - 12

SP - 4521

EP - 4530

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 10

ER -