Medizinische Universität Graz - Research portal
Selected Publication:
BECKER, JC; CZERNY, C; BROCKER, EB.
Maintenance of clonal anergy by endogenously produced IL-10.
Int Immunol. 1994; 6(10):1605-1612
Doi: 10.1093/intimm/6.10.1605
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- Leading authors Med Uni Graz
- Becker Jürgen Christian
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- Abstract:
- Inadequate co-stimulation of tumor reactive T cells may contribute to the fact that antigenic tumors are not normally rejected by the immune system. We recently reported that the induction of profound unresponsiveness in a T cell clone by melanoma cells expressing MHC class II antigens may provide a mechanism for these tumor cells to escape immunosurveillance. Here we demonstrate that two T cell clones (sTC3 and sTS5) produced high amounts of IL-10 after being rendered anergic by autologous melanoma cells. Co-culture of these T cell clones with melanoma cell transfectants expressing B7, which failed to induce anergy, resulted in a significantly lower production of IL-10. IL-10 production by the anergic T cell clones correlated with an impaired ability to produce IL-2 in response to TCR mediated activation. Neutralization of IL-10 reduced the duration of T cell unresponsiveness from 14 to only 4 days, but inhibition of IL-10 production during initiation of anergy showed no effect on it. Induction of the unresponsive state, as well as the subsequent IL-10 production in sTC3 cells, could be prevented by the addition of cyclosporin A to the primary co-culture of sTC3 and the autologous melanoma. Taken together, these results indicate that IL-10 is important for maintenance of T cell anergy induced by contact with nonprofessional antigen presenting cells such as MHC class II+ melanoma cells. Furthermore, we were able to detect IL-10 in serum from melanoma patients and IL-10 mRNA in tumor infiltrating lymphocytes isolated from melanoma metastases, suggesting an in vivo relevance of our in vitro findings.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, CD3 - immunology
- Base Sequence -
- Clonal Anergy - immunology
- Clone Cells -
- HLA-D Antigens - immunology
- Humans -
- Interleukin-10 - biosynthesis Interleukin-10 - immunology
- Lymphocytes, Tumor-Infiltrating - immunology
- Melanoma - immunology
- Molecular Sequence Data -
- Polymerase Chain Reaction -
- T-Lymphocytes - immunology
- Tumor Cells, Cultured - immunology
- Find related publications in this database (Keywords)
- CLONAL ANERGY
- IL-10