Inhibition of proliferation and CD25 down-regulation by retinoic acid in human adult T cell leukemia cells

Abstract

The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptors (IL-2Rα/p55, Tac, CD25) by the human 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 (ATRA) resulted in marked inhibition of cell growth, determined by ³H-thymidine incorporation, and in down-regulation of CD25 expression, determined 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 MOLT-4) and in normal lymphocytes that had been stimulated with phytohemagglutinin or phorbol 12-myristate 13-acetate. We have shown that RA markedly inhibited both the cell growth and the expression of CD25 in some 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).