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: Patric M Schiltz, German G Gomez, Susana B Read, Nisha V Kulprathipanja, Carol A Kruse
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 22 Issue 12 Pg. 1209-16 (Dec 2002) ISSN: 1079-9907 [Print] United States
• PMID: 12581494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Interleukin-1
• Isoantigens
• Intercellular Adhesion Molecule-1
• Interferon-gamma

Topics

• Animals
• Brain Neoplasms
• Cytotoxicity, Immunologic
• Gliosarcoma
• Histocompatibility Antigens Class I (genetics)
• Histocompatibility Antigens Class II (genetics)
• Intercellular Adhesion Molecule-1 (genetics)
• Interferon-gamma (pharmacology)
• Interleukin-1 (pharmacology)
• Isoantigens (immunology)
• Major Histocompatibility Complex
• Rats
• Rats, Inbred F344
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured