| First Author | Cheng X | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 6 | Pages | 2735-41 |
| PubMed ID | 9510174 | Mgi Jnum | J:46189 |
| Mgi Id | MGI:1197332 | Doi | 10.4049/jimmunol.160.6.2735 |
| Citation | Cheng X, et al. (1998) CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down- regulated production of IFN-gamma: role of phosphatidyl serine. J Immunol 160(6):2735-41 |
| abstractText | IFN-gamma production is dramatically reduced in T cells from mice bearing large mammary tumors. This inhibition of IFN-gamma 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-gamma 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-gamma production of CD4+, but not that of CD8+, T cells. Methylation analysis indicated that the CpG dinucleotide in SnaBI site of the IFN-gamma 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-gamma 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-gamma production can be regulated independently from that of other type 1 cytokines in vivo. Our data further suggest that PS is involved in IFN-gamma gene down-regulation during mammary tumorigenesis and contributes to the generalized immunosuppression associated with tumor growth. |
