Expression of increased immunogenicity by thiol-releasing tumor variants
- Authors
- 임종석; Hans-Peter Eck; HelmutGmünder; WulfDröge
- Issue Date
- Apr-1992
- Publisher
- Academic Press
- Citation
- Cellular Immunology, v.140, no.2, pp 345 - 356
- Pages
- 12
- Journal Title
- Cellular Immunology
- Volume
- 140
- Number
- 2
- Start Page
- 345
- End Page
- 356
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/151118
- DOI
- 10.1016/0008-8749(92)90201-Y
- ISSN
- 0008-8749
- Abstract
- Even moderate variations of the extracellular cysteine concentration were previously shown to affect T cell functions in vitro despite high concentrations of cystine. We therefore analyzed the membrane transport activities of T cells for cysteine and cystine, and the role of low molecular weight thiol in T cell-mediated host responses against a T cell tumor in vivo. A series of T cell clones and tumors including the highly malignant lymphoma L5178Y ESb and its strongly immunogenic variant ESb-D was found to express extremely weak transport activity for cystine but strong transport activity for cysteine. However, not all cells showed the expected requirement for cysteine (or 2-mercaptoethanol (2-ME)) in the culture medium. One group of clones and tumors including the malignant ESb-lymphoma did not respond to changes of extracellular cystine concentrations and was strongly thiol dependent. This group released only little acid soluble thiol (cysteine) if grown in cystine-containing cultures. The other T cell lines, in contrast, were able to maintain high intracellular GSH levels and DNA synthesis activity in cystine-containing culture medium without cysteine or 2-ME and released substantial amounts of thiol. This group included the immunogenic ESb-D line. Additional thiol-releasing ESb variants were obtained by culturing large numbers of L5178Y ESb tumor cells in cultures without cysteine or 2-ME. All of these ESb variants showed a significantly decreased tumcrigenicity and some of them induced cytotoxic and protective host responses even against the malignant ESb parent tumor. Taken together, our experiments suggest that the host response against a tumor may be limited in certain cases by the failure of the stimulator (i.e., the tumor) cell to deliver sufficient amounts of cysteine to the responding T cells.
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