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 language | English |
|---|---|
| Pages (from-to) | 2735-2741 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 160 |
| Issue number | 6 |
| State | Published - Mar 15 1998 |
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- 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 journal › Article
}
TY - JOUR
T1 - CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-γ
T2 - Role of phosphatidyl serine
AU - Cheng, Xiaofang
AU - Lopez, Diana M
PY - 1998/3/15
Y1 - 1998/3/15
N2 - 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.
AB - 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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M3 - Article
VL - 160
SP - 2735
EP - 2741
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -