ABSTRACT
No abstract available.
Subject(s)
Cytokines/pharmacology , Gene Expression Regulation , Genes, MHC Class I , Histocompatibility Antigens Class I/biosynthesis , Interferons/pharmacology , Lymphotoxin-alpha/pharmacology , Models, Genetic , Signal Transduction , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
A soluble factor which augments the expression of major histocompatibility complex class I (MHC I) antigens on a number of murine tumor cell lines, has been isolated from the culture supernatants of mixed lymphocyte reaction of spleen cells derived from C57B1/6, Balb/c and Swiss mice. The factor, termed MHC-augmenting factor (MHC-AF) has been partially purified by Sephadex G-100 column chromatography and reverse phase HPLC. MHC-AF activity is associated with an 18 kDa molecule. MHC-AF activity was resistant to pH 2.0 treatment and partially purified MHC-AF preparations did not have any activity in L929 cell/vesicular stomatitis virus (VSV) interferon bioassay system. Antibodies to IFN-gamma did not block the activity of MHC-AF. These results indicate that a MHC-AF distinct from IFN-gamma, is produced by mouse spleen cells undergoing a mixed lymphocyte reaction.
Subject(s)
Mice , Animals , Antibodies/pharmacology , Chymotrypsin/metabolism , Chymotrypsin/chemistry , Comparative Study , Concanavalin A/pharmacology , Hot Temperature , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class I/drug effects , Interferon-gamma/pharmacology , Interferon-gamma/metabolism , Interferon-gamma/immunology , Lymphocytes/physiology , Mice, Inbred BALB C , Mice, Inbred C57BL , Proteins/pharmacology , Proteins/metabolism , Proteins/isolation & purification , Spleen/cytology , Trypsin/metabolism , Trypsin/chemistry , Tumor Cells, Cultured/immunology , Tumor Cells, Cultured/drug effectsABSTRACT
Mouse spleen cells activated in a mixed lymphocyte reaction release a soluble factor, which induces a significant proliferative response in fresh mouse spleen cells. This proliferation inducing factor (PIF) was found to be heat stable (90 degrees C for 45 min) and also resistant to trypsin or chymotrypsin treatment. By using a sizing HPLC column, the molecular weight of PIF appears to be 25 kDa. Mouse spleen cells treated with anti-thy-1 + complement lost Con-A induced proliferative responses but responded well to PIF. B cell depleted spleen cells obtained by negative selection panning, did not respond to PIF. These results indicate that B cells proliferated in response to PIF. Polymixin-B, which blocks the B cell proliferative response to LPS, did not inhibit PIF induced proliferation.
Subject(s)
Mice , Animals , B-Lymphocytes/physiology , B-Lymphocytes/drug effects , Bone Marrow/metabolism , Cell Division/physiology , Chromatography, High Pressure Liquid , Chymotrypsin/pharmacology , Dose-Response Relationship, Drug , Growth Substances/pharmacology , Growth Substances/chemistry , Hot Temperature , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Weight , Polymyxin B/pharmacology , Protein Denaturation , Spleen/metabolism , Thymus Gland/metabolism , Trypsin/pharmacologyABSTRACT
A novel factor which augments the expression of major histocompatibility complex I (MHC augmenting factor or MHC-AF) antigens on tumor cell lines, has been isolated from the culture supernatants of human peripheral blood mononuclear cells activated by concanavalin-A. A mouse equivalent of this factor has also been isolated from the culture supernatants of mouse spleen cells activated by mitogens or in a mixed lymphocyte reaction. Mouse MHC-AF enhances the expression of class I MHC antigens on murine tumor cell lines (EL-4 and BW5147) but not on human tumor cell lines (K562 and HR-7). Human MHC-AF on the other hand enhances the MHC I expression on both human as well as murine cell lines. Interferon gamma (IFN-gamma), a cytokine also known to enhance the expression of MHC I antigens, acts in a highly species specific manner with mouse IFN-gamma augmenting the MHC I on murine tumor cell lines and human IFN-gamma augmenting the MHC I on human tumor cell lines only. These results indicate important differences in the cross species biological activities of MHC-AF and IFN-gamma, and provide additional evidence for MHC-AF being distinct from IFN-gamma.