title: Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.
abstract: To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA.
authors.forename: Patric M
authors.initials: PM
authors.lastname: Schiltz
authors.forename: German G
authors.initials: GG
authors.lastname: Gomez
authors.forename: Susana B
authors.initials: SB
authors.lastname: Read
authors.forename: Nisha V
authors.initials: NV
authors.lastname: Kulprathipanja
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kruse
mesh_terms: D000818:Animals; D001932:Brain Neoplasms; D003602:Cytotoxicity, Immunologic; D018316:Gliosarcoma; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D008285:Major Histocompatibility Complex; D051381:Rats; D011916:Rats, Inbred F344; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007519:Isoantigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma