Altered CD3 chain and cytokine gene expression in tumor infiltrating T lymphocytes during the development of mesothelioma.
The mechanisms whereby tumors escape immunosurveillance remain poorly understood. De-activation or deviation of T lymphocyte responses may occur following exposure to tumor-associated or -derived signals. In the present study it is demonstrated that during development of syngeneic malignant mesothelioma in mice, the relative CD3 delta, CD3 gamma and CD3 zeta mRNA levels expressed by tumor infiltrating lymphocytes (TIL) decrease, while CD3 epsilon mRNA levels remain relatively constant. Expression of IFN gamma mRNA by TIL decreased during tumor development, while IL-2 mRNA levels showed slight increases. IL-3 mRNA was not detected at any time during tumor development and IL-4 transcripts were detected in the later stages of tumor development. In the spleens of tumor-bearing mice, IL-2 transcripts were detected throughout the time course from days 1 to 22(24), while IFN gamma mRNA was only detected at early times from days 0-13. Previous work demonstrated a role for tumor cell-derived TGF beta in the immunobiology of mesothelioma. Here it is shown that the suppression of CD3-subunit expression by TIL was ameliorated in tumors where TGF beta -expression was reduced by inducible TGF beta-specific antisense-RNA, thus, suggesting that lymphocytes may become de-activated upon infiltration of the tumor micro-environment.
Jarnicki
A G
AG
University of Western Ausralia Department of Medicine, QE II Medical Centre, Nedlands, Australia.
Fitzpatrick
D R
DR
Robinson
B W
BW
Bielefeldt-Ohmann
H
H
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D046911:Macromolecular Substances; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology
D016207:Cytokines; D017931:DNA Primers; D007377:Interleukin-3; D046911:Macromolecular Substances; D016372:RNA, Antisense; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma