Maintenance of clonal anergy by endogenously produced IL-10.

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.

journal_name

Int Immunol

journal_title

International immunology

authors

Becker JC,Czerny C,Bröcker EB

doi

10.1093/intimm/6.10.1605

subject

Has Abstract

pub_date

1994-10-01 00:00:00

pages

1605-12

issue

10

eissn

0953-8178

issn

1460-2377

journal_volume

6

pub_type

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