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Differential Susceptibility of HLA Class II Antigens Induced by -Interferon in Human Neuroblastoma Cell Lines¹

Children's Research Hospital [T. Su.], Departments of Pediatrics [T. Su., Y. H., T. H., H. K., T. Sa.] and Microbiology [J. I.], and Laboratory of Electron Microscopy [H. M.], Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602, Japan; Department of Transplantation, School of Medicine, Tokai University, Kanagawa 259-11, Japan [H. I.]; and Institute of Child Health, London WC1 1EH, England [J. T. K.]

Five neuroblastoma cell lines have been examined for the induction of HLA class II antigens by a recombinant -interferon. The expression of HLA-DR and -DP was induced on up to 80% of cells in two of five neuroblastoma cell lines examined (KP-N-SI and KP-N-RT). Low expression of HLA-DR and -DP was induced on the SK-N-DZ line in the presence of recombinant -interferon for 10 days. In contrast HLA-DQ was not induced on any of five neuroblastoma cell lines studied. HLA-DR and -DP antigen induction was reversible, falling to nondetectable levels when interferon was removed from the culture medium. The reinduction of interferon to the culture medium again induced HLA-DR and -DP antigen expression in a fashion similar to that originally observed. These results were confirmed by Northern blot analysis using a probe to HLA-DR mRNA. Recombinant interferon appears to induce HLA class II expression at the level of gene transcription or posttranscription. The results also indicate that HLA-DR, -DP, and -DQ antigens are independently regulated.

Treatment of neuroblastoma cell lines with -interferon results in the induction of a differentiated phenotype. Although the cytokine -interferon induces neurofilament expression in some of the cell lines, this was not the case for all lines studied. Thus no correlation could be established between the morphological differentiation and either HLA class II or neurofilament expression. In addition, no correlation between response to recombinant interferon and N-myc amplification was noted. The biological significance of HLA class II expression on neuroblastoma cell lines by -interferon may be related to the differentiation stage of neuroblastoma cells or may enable -interferon-treated neuroblastoma cells to be recognized by cytotoxic T-cells.

¹ This work was supported in part by grants for Cancer Research from the Ministry of Health and Welfare of Japan; from the Ministry of Education, Science and Culture (63480238); from the Mochida Memorial Foundation for Medical Research; from the Association for Osaka Cancer Research; and from the Association for Childhood Cancer Research of Japan.

² To whom requests for reprints should be addressed, at Department of Pediatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602, Japan.

Received 9/ 7/88. Revised 12/27/88. Accepted 1/ 4/89.

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