Taurine attenuates CD3/interleukin‐2‐induced T cell apoptosis in an in vitro model of activation‐induced cell death (AICD)

Summary Interleukin (IL)‐2 immunotherapy is used for the treatment of metastatic melanoma and renal cell carcinoma and mediates its effects through the clonal expansion of lymphocytes. Although IL‐2 remains the most effective form of therapy for these cancers, response rates are poor and dose escala...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical and experimental immunology Vol. 139; no. 2; pp. 279 - 286
Main Authors:	Maher, S. G., Condron, C. E M., Bouchier‐Hayes, D. J., Toomey, D. M.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Science Ltd 01-02-2005 Blackwell Oxford University Press Blackwell Science Inc
Subjects:	Analysis of Variance Antibodies, Monoclonal - pharmacology Apoptosis - drug effects Biological and medical sciences CD3 Complex - immunology CD3 Complex - pharmacology Fas Ligand Protein FasL Flow Cytometry Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunopathology Immunotherapy Interleukin-2 - immunology Interleukin-2 - pharmacology interleukin‐2 Jurkat Cells Medical sciences Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - metabolism Neoplasms - therapy NF-kappa B - metabolism nuclear factor kappa‐B Original T cell T-Lymphocytes - immunology T-Lymphocytes - pathology taurine Taurine - pharmacology Immunopathology Fas ligand Taurine interleukin-2 T cell Cytokine In vitro Immunology Interleukin 2 Cell death FasL Aminoacid T-Lymphocyte nuclear factor kappa-B Models Transcription factor Apoptosis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Summary Interleukin (IL)‐2 immunotherapy is used for the treatment of metastatic melanoma and renal cell carcinoma and mediates its effects through the clonal expansion of lymphocytes. Although IL‐2 remains the most effective form of therapy for these cancers, response rates are poor and dose escalation is hampered by side effects, which include vascular leak and lymphopenia. The mechanism underlying T cell loss is currently unidentified but could be the induction of activation‐induced cell death (AICD) mediated by FasL. Our previous studies have shown that the amino acid taurine can attenuate apoptosis induced by a number of factors in different cell types. Here, we induced T cell AICD via CD3 and IL‐2 stimulation and investigated the effect of taurine on lymphocyte apoptosis. Anti‐CD3‐activated Jurkat T cells treated with IL‐2 significantly increased FasL expression, which was associated with increased apoptosis. Treatment with taurine prior to stimulation down‐regulated FasL protein expression and partially inhibited apoptosis. Inhibition of FasL‐signalling resulted in an identical reduction in apoptosis. As the kinetics of AICD are completely different in circulating T cells, we repeated these experiments in such cells to confirm our finding. Stimulation of CD4+ circulating T cells induced apoptosis in sensitized, but not freshly isolated T cells, which was abrogated partially by taurine. In Jurkat cells it was determined that taurine‐mediated down‐regulation of FasL protein expression was associated with decreased FasL mRNA expression and reduced NFκB activation. These results reveal one possible mechanism underlying the lymphopenia observed with IL‐2 immunotherapy, involving increased FasL expression leading to apoptosis. Taurine may be of use in reversing the lymphopenia associated with IL‐2, thereby augmenting its immunotherapeutic potential.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0009-9104 1365-2249
DOI:	10.1111/j.1365-2249.2005.02694.x