CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-γ: Role of phosphatidyl serine

Xiaofang Cheng, Diana M Lopez

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

IFN-γ production is dramatically reduced in T cells from mice bearing large mammary tumors. This inhibition of IFN-γ gene expression occurs mostly in CD4+ T cells, as determined by ELISA and reverse transcriptase-PCR. The effects of known mammary tumor factors in normal T cells and its subsets were evaluated. Pretreatment with granulocyte-macrophage CSF resulted in increased IFN-γ levels by T cells, while PGE2 pretreatment equally decreased the levels of this cytokine in CD4+ and CD8+ T cells from normal mice. Interestingly, phosphatidyl serine (PS) down-regulated the IFN-γ production of CD4+, but not that of CD8+, T cells. Methylation analysis indicated that the CpG dinucleotide in SnaBI site of the IFN-γ, 5' promoter flank region was hypermethylated in CD4+, but not in CD8+, T cells of large tumor bearers and of normal mice pretreated with PS. Electrophoresis mobility shift assay using an oligonucleotide probe corresponding to the IFN-γ, promoter core region sequence showed a greatly reduced binding of a 90-kDa nuclear protein in CD4+ T cells from tumor bearers and in those from PS-pretreated normal mice. Since IL-2 production is not affected in either CD4+ or CD8+ T cells from tumor bearers, these studies indicate that IFN-γ, production can be regulated independently from that of other type 1 cytokines in vivo. Our data further suggest that PS is involved in IFN-γ gene down-regulation during mammary tumorigenesis and contributes to the generalized immunosuppression associated with tumor growth.

Original languageEnglish
Pages (from-to)2735-2741
Number of pages7
JournalJournal of Immunology
Volume160
Issue number6
StatePublished - Mar 15 1998

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Phosphatidylserines
Breast Neoplasms
T-Lymphocytes
Genetic Promoter Regions
Neoplasms
Cytokines
Oligonucleotide Probes
T-Lymphocyte Subsets
Electrophoretic Mobility Shift Assay
Nuclear Proteins
Reverse Transcriptase Polymerase Chain Reaction
Dinoprostone
Granulocytes
Immunosuppression
Methylation
Interleukin-2
Electrophoresis
Carcinogenesis
Breast
Down-Regulation

ASJC Scopus subject areas

  • Immunology

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CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-γ : Role of phosphatidyl serine. / Cheng, Xiaofang; Lopez, Diana M.

In: Journal of Immunology, Vol. 160, No. 6, 15.03.1998, p. 2735-2741.

Research output: Contribution to journalArticle

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abstract = "IFN-γ production is dramatically reduced in T cells from mice bearing large mammary tumors. This inhibition of IFN-γ gene expression occurs mostly in CD4+ T cells, as determined by ELISA and reverse transcriptase-PCR. The effects of known mammary tumor factors in normal T cells and its subsets were evaluated. Pretreatment with granulocyte-macrophage CSF resulted in increased IFN-γ levels by T cells, while PGE2 pretreatment equally decreased the levels of this cytokine in CD4+ and CD8+ T cells from normal mice. Interestingly, phosphatidyl serine (PS) down-regulated the IFN-γ production of CD4+, but not that of CD8+, T cells. Methylation analysis indicated that the CpG dinucleotide in SnaBI site of the IFN-γ, 5' promoter flank region was hypermethylated in CD4+, but not in CD8+, T cells of large tumor bearers and of normal mice pretreated with PS. Electrophoresis mobility shift assay using an oligonucleotide probe corresponding to the IFN-γ, promoter core region sequence showed a greatly reduced binding of a 90-kDa nuclear protein in CD4+ T cells from tumor bearers and in those from PS-pretreated normal mice. Since IL-2 production is not affected in either CD4+ or CD8+ T cells from tumor bearers, these studies indicate that IFN-γ, production can be regulated independently from that of other type 1 cytokines in vivo. Our data further suggest that PS is involved in IFN-γ gene down-regulation during mammary tumorigenesis and contributes to the generalized immunosuppression associated with tumor growth.",
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