INHIBITION OF PROLIFERATION AND CD25 DOWN-REGULATION BY RETINOIC ACIDIN HUMAN ADULT T-CELL LEUKEMIA-CELLS

The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptors (IL-2R alpha/p55, Tac, CD25) by the hu man T lymphotropic virus type I (HTLV-I)-positive T cell lines, HUT102 and ATL-2 were investigated. Incubation of these cells for 48 h with either 13-cis retinoid acid (13-cis RA) or all-trans retinoic acid (AT RA) resulted in marked inhibition of cell growth, determined by H-3-th ymidine incorporation, and in down-regulation of CD25 expression, dete rmined by flow cytometry. Four HUT102 cell clones were established by limiting dilution, and 13 cis RA was shown to inhibit cell growth and CD25 expression in three of these clones (HUT102-M5, -M6 and -M7), but not in the fourth (-M8). RA did not induce growth inhibition or down- regulation of CD25 in the HTLV-I-negative T cell lines (Jurkat and MOL T-4) and in normal lymphocytes that had been stimulated with phytohema gglutinin or phorbol 12-myristate 13-acetate. We have shown that RA ma rkedly inhibited both the cell growth and the expression of CD25 in so me HTLV-I-positive T cell clones, but not in normal lymphocytes. These results suggest that RA may be suitable for the treatment of patients with adult T cell leukemia (ATL).