Transforming growth factor-β down-regulates major histocompatibility complex class I antigen expression and increases the susceptibility of uveal melanoma cells to natural killer cell-mediated cytolysis

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Abstract

Intraocular melanomas, especially those of the anterior segment, reside within an immunologically privileged milieu. Aqueous humour contains a variety of immunomodulatory factors that are believed to contribute to ocular immune privilege. Among these is transforming growth factor-β (TGF-β), which has been shown to down-regulate major histocompatibility complex (MHC) class I antigens on normal cells. Since the susceptibility of tumour cells to natural killer (NK) cell-mediated lysis is inversely correlated with the expression of MHC class I antigens, tumour cells exposed to TGF-β might be ted to experience enhanced susceptibility to NK-mediated killing. This was examined by incubating two human uveal melanoma cell lines in the presence of TGF-β and evaluating the expression of MHC class I antigen and susceptibility to NK cell-mediated lysis. OCM1 and OCM8 melanoma cells constitutively express high levels of class I antigen (85-90% positive) and low susceptibility to NK-mediated lysis in vitro (3-8%). Incubation with TGF-β produced a significant reduction in class I antigen expression (52-62%) and a proportional increased susceptibility to NK cell-mediated cytolysis (17%). Analogous effects were found using a human uveal melanoma cell line (OCM3) that constitutively expresses low amounts of class I (<5% positive) and high NK susceptibility (35% lysis). Stimulation of class I antigen expression by incubation with interferon-γ resulted in a sharp increase in class I expression (80% positive) and a comparable diminution in susceptibility to NK cell-mediated lysis (<10%). The results indicate that TGF-β, at concentrations found in the aqueous humour, can significantly alter MHC class I antigen expression and the susceptibility of ocular melanoma cells to NK cell-mediated cytolysis.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalImmunology
Volume86
Issue number2
StatePublished - 1995

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Histocompatibility Antigens Class I
Transforming Growth Factors
Major Histocompatibility Complex
Natural Killer Cells
Down-Regulation
Melanoma
Aqueous Humor
Cell Line
Uveal melanoma
Interferons
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Transforming growth factor-β down-regulates major histocompatibility complex class I antigen expression and increases the susceptibility of uveal melanoma cells to natural killer cell-mediated cytolysis",
abstract = "Intraocular melanomas, especially those of the anterior segment, reside within an immunologically privileged milieu. Aqueous humour contains a variety of immunomodulatory factors that are believed to contribute to ocular immune privilege. Among these is transforming growth factor-β (TGF-β), which has been shown to down-regulate major histocompatibility complex (MHC) class I antigens on normal cells. Since the susceptibility of tumour cells to natural killer (NK) cell-mediated lysis is inversely correlated with the expression of MHC class I antigens, tumour cells exposed to TGF-β might be ted to experience enhanced susceptibility to NK-mediated killing. This was examined by incubating two human uveal melanoma cell lines in the presence of TGF-β and evaluating the expression of MHC class I antigen and susceptibility to NK cell-mediated lysis. OCM1 and OCM8 melanoma cells constitutively express high levels of class I antigen (85-90{\%} positive) and low susceptibility to NK-mediated lysis in vitro (3-8{\%}). Incubation with TGF-β produced a significant reduction in class I antigen expression (52-62{\%}) and a proportional increased susceptibility to NK cell-mediated cytolysis (17{\%}). Analogous effects were found using a human uveal melanoma cell line (OCM3) that constitutively expresses low amounts of class I (<5{\%} positive) and high NK susceptibility (35{\%} lysis). Stimulation of class I antigen expression by incubation with interferon-γ resulted in a sharp increase in class I expression (80{\%} positive) and a comparable diminution in susceptibility to NK cell-mediated lysis (<10{\%}). The results indicate that TGF-β, at concentrations found in the aqueous humour, can significantly alter MHC class I antigen expression and the susceptibility of ocular melanoma cells to NK cell-mediated cytolysis.",
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T1 - Transforming growth factor-β down-regulates major histocompatibility complex class I antigen expression and increases the susceptibility of uveal melanoma cells to natural killer cell-mediated cytolysis

AU - Ma, D.

AU - Niederkorn, J. Y.

PY - 1995

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N2 - Intraocular melanomas, especially those of the anterior segment, reside within an immunologically privileged milieu. Aqueous humour contains a variety of immunomodulatory factors that are believed to contribute to ocular immune privilege. Among these is transforming growth factor-β (TGF-β), which has been shown to down-regulate major histocompatibility complex (MHC) class I antigens on normal cells. Since the susceptibility of tumour cells to natural killer (NK) cell-mediated lysis is inversely correlated with the expression of MHC class I antigens, tumour cells exposed to TGF-β might be ted to experience enhanced susceptibility to NK-mediated killing. This was examined by incubating two human uveal melanoma cell lines in the presence of TGF-β and evaluating the expression of MHC class I antigen and susceptibility to NK cell-mediated lysis. OCM1 and OCM8 melanoma cells constitutively express high levels of class I antigen (85-90% positive) and low susceptibility to NK-mediated lysis in vitro (3-8%). Incubation with TGF-β produced a significant reduction in class I antigen expression (52-62%) and a proportional increased susceptibility to NK cell-mediated cytolysis (17%). Analogous effects were found using a human uveal melanoma cell line (OCM3) that constitutively expresses low amounts of class I (<5% positive) and high NK susceptibility (35% lysis). Stimulation of class I antigen expression by incubation with interferon-γ resulted in a sharp increase in class I expression (80% positive) and a comparable diminution in susceptibility to NK cell-mediated lysis (<10%). The results indicate that TGF-β, at concentrations found in the aqueous humour, can significantly alter MHC class I antigen expression and the susceptibility of ocular melanoma cells to NK cell-mediated cytolysis.

AB - Intraocular melanomas, especially those of the anterior segment, reside within an immunologically privileged milieu. Aqueous humour contains a variety of immunomodulatory factors that are believed to contribute to ocular immune privilege. Among these is transforming growth factor-β (TGF-β), which has been shown to down-regulate major histocompatibility complex (MHC) class I antigens on normal cells. Since the susceptibility of tumour cells to natural killer (NK) cell-mediated lysis is inversely correlated with the expression of MHC class I antigens, tumour cells exposed to TGF-β might be ted to experience enhanced susceptibility to NK-mediated killing. This was examined by incubating two human uveal melanoma cell lines in the presence of TGF-β and evaluating the expression of MHC class I antigen and susceptibility to NK cell-mediated lysis. OCM1 and OCM8 melanoma cells constitutively express high levels of class I antigen (85-90% positive) and low susceptibility to NK-mediated lysis in vitro (3-8%). Incubation with TGF-β produced a significant reduction in class I antigen expression (52-62%) and a proportional increased susceptibility to NK cell-mediated cytolysis (17%). Analogous effects were found using a human uveal melanoma cell line (OCM3) that constitutively expresses low amounts of class I (<5% positive) and high NK susceptibility (35% lysis). Stimulation of class I antigen expression by incubation with interferon-γ resulted in a sharp increase in class I expression (80% positive) and a comparable diminution in susceptibility to NK cell-mediated lysis (<10%). The results indicate that TGF-β, at concentrations found in the aqueous humour, can significantly alter MHC class I antigen expression and the susceptibility of ocular melanoma cells to NK cell-mediated cytolysis.

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