Document Detail

CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-gamma: role of phosphatidyl serine.
MedLine Citation:
PMID:  9510174     Owner:  NLM     Status:  MEDLINE    
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.
X Cheng; D M Lopez
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  160     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-03-26     Completed Date:  1998-03-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2735-41     Citation Subset:  AIM; IM; X    
Department of Microbiology and Immunology, University of Miami School of Medicine, and the Sylvester Cancer Center, FL 33101, USA.
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MeSH Terms
CD4-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / metabolism*
DNA Methylation
Interferon-gamma / biosynthesis*,  genetics
Mammary Neoplasms, Experimental / immunology*
Mice, Inbred BALB C
Phosphatidylserines / pharmacology*
RNA, Messenger / analysis
Grant Support
Reg. No./Substance:
0/Phosphatidylserines; 0/RNA, Messenger; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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