Tumor-induced interleukin 10 suppresses the ability of splenic Dendritic Cells to stimulate CD4 and CD8 T-cell responses

Arvin S. Yang, Edmund Lattime

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Dendritic cell (DC) maturation and function are influenced by the surrounding cytokine milieu. We demonstrate tumor-associated suppression of DCs in stimulating allogeneic and tumor-specific CTL and type 1 (IFN-γ-producing) responses in both CD4- and CD8-positive T cells. DCs from MB49-bearing female mice fail to stimulate proliferative and IFN-γ-producing responses in allogeneic mixed lymphocyte cultures. MB49 also inhibited DC function in stimulating type 1 responses against our tumor-specific antigen, the male antigen, HY. DCs from MB49-bearing male mice were unable to restimulate effective HY-specific CTLs or IFN-γ. Tumor-induced interleukin (IL) 10 was found to be specifically responsible for DC dysfunction in response to antigenic driven maturation. This was demonstrated by restoration of DC function in splenic DCs from MB49-bearing female IL-10 knockout mice (HY disparity), whereas not in MB49-bearing male IL-10 knockout mice (no HY disparity). Finally, any tumor-induced systemic inhibitory effect on bone marrow precursors could be overcome by generation of bone marrow-derived DCs ex vivo. These bone marrow-derived DCs derived from MB49-bearing B6 mice were capable of inducing control levels of proliferation in allogeneic mixed lymphocyte reactions and a type 1 (IFN-γ) cytokine profile. The BM-DCs were also capable of restimulating HY-specific CTL and IFN-γ production. These studies reveal the tumor-associated in vivo effects of IL-10 inhibition on DC function in eliciting a type 1 immune response in both allogeneic and tumor-specific responses.

Original languageEnglish (US)
Pages (from-to)2150-2157
Number of pages8
JournalCancer Research
Volume63
Issue number9
StatePublished - May 1 2003

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Interleukin-10
Dendritic Cells
T-Lymphocytes
Neoplasms
Bone Marrow
Knockout Mice
H-Y Antigen
Cytokines
Mixed Lymphocyte Culture Test
Neoplasm Antigens
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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abstract = "Dendritic cell (DC) maturation and function are influenced by the surrounding cytokine milieu. We demonstrate tumor-associated suppression of DCs in stimulating allogeneic and tumor-specific CTL and type 1 (IFN-γ-producing) responses in both CD4- and CD8-positive T cells. DCs from MB49-bearing female mice fail to stimulate proliferative and IFN-γ-producing responses in allogeneic mixed lymphocyte cultures. MB49 also inhibited DC function in stimulating type 1 responses against our tumor-specific antigen, the male antigen, HY. DCs from MB49-bearing male mice were unable to restimulate effective HY-specific CTLs or IFN-γ. Tumor-induced interleukin (IL) 10 was found to be specifically responsible for DC dysfunction in response to antigenic driven maturation. This was demonstrated by restoration of DC function in splenic DCs from MB49-bearing female IL-10 knockout mice (HY disparity), whereas not in MB49-bearing male IL-10 knockout mice (no HY disparity). Finally, any tumor-induced systemic inhibitory effect on bone marrow precursors could be overcome by generation of bone marrow-derived DCs ex vivo. These bone marrow-derived DCs derived from MB49-bearing B6 mice were capable of inducing control levels of proliferation in allogeneic mixed lymphocyte reactions and a type 1 (IFN-γ) cytokine profile. The BM-DCs were also capable of restimulating HY-specific CTL and IFN-γ production. These studies reveal the tumor-associated in vivo effects of IL-10 inhibition on DC function in eliciting a type 1 immune response in both allogeneic and tumor-specific responses.",
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Tumor-induced interleukin 10 suppresses the ability of splenic Dendritic Cells to stimulate CD4 and CD8 T-cell responses. / Yang, Arvin S.; Lattime, Edmund.

In: Cancer Research, Vol. 63, No. 9, 01.05.2003, p. 2150-2157.

Research output: Contribution to journalArticle

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