Induction of ICAM‐1 and LFA‐3 by Tax1 of human T‐cell leukemia virus type 1 and mechanism of down‐regulation of ICAM‐1 or LFA‐1 in adult‐T‐cell‐leukemia cell lines

The present study was undertaken to determine the role of HTLV‐I TaxI in the up‐regulation of ICAM‐1 and LFA‐3 in human T cells transformed with HTLV‐I and the mechanism of down‐regulation of ICAM‐1 and LFA‐I in ATL‐derived cell lines. Induction of Taxl in a human T‐cell line Jurkat carrying the Taxi gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM‐1. The response of LFA‐3 to Taxl induction was, on the other hand, relatively slow and weak, and might be indirect. Transactivation of the ICAM‐1 promoter by Taxl was further shown by co‐transfection of a CAT reporter construct with the ICAM‐1 promoter and a plasmid expressing Taxl. The mechanism of down‐regulation of ICAM‐1 or LFA‐1 in 4 ATL cell lines was next examined. ICAM‐1 mRNA was quite low in MT‐1, but no genomic changes were found. The CAT reporter with the ICAM‐1 promoter was inactive in MT‐1. Finally, combined treatment of MT‐1 with 5‐azacytidine and IFN‐γ induced re‐expression of ICAM‐1. Collectively, (a) transcriptional factor(s) necessary for expression of ICAM‐1 gene may be repressed in MT‐1 through DNA methylation. Three other ATL cell lines (TL‐Oml, H582, HuT 102) were found to have little mRNA for the LFA‐1 β chain (CD 18). H582 and HuT 102 were also negative for the LFA‐1 α chain (CDI la) mRNA. No genomic changes were found, and a CAT reporter gene with the CD 18 promoter was inactive in the 3 of them, again suggesting lack of (a) transcriptional factor(s) necessary for CD 18 expression.