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 OF LFA-1 IN ADULT-T-CELL-LEUKEMIA CELL-LINES

The present study was undertaken to determine the role of HTLV-I Tax1 in the up-regulation of ICAM-1 and LFA-3 in human T cells transformed with HTLV-1 and the mechanism of down-regulation of ICAM-1 and LFA-1 in ATL-derived cell lines. Induction of Tax1 in a human T-cell line jurkat carrying the Tax1 gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM-1. The response of LFA-3 to Tax1 induction was, on the other hand, relatively slow and weak, and might be indirect. Transactivation of the ICAM-1 promoter by Tax1 was further shown by co-transfection of a CAT reporter construct with the ICAM-1 promoter and a plasmid expressing Tax1. 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-I with 5-azacytidine and IFP-gamma 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, HuT102) were found to have little mRNA for the LFA-1 beta chain (CD18). H582 and HuT102 were also negative for the LFA-1 alpha chain (CD11a) mRNA. No genomic changes were found, and a CAT reporter gene with the CD18 promoter was inactive in the 3 of them, again suggesting lack of (a) transcriptional factor(s) necessary for CD18 expression. (C) 1995 Wiley-Liss, Inc.