Selection of HTLV-1 positive clones is prevented by prostaglandin A in infected cord blood cultures

Type A prostaglandins (PGA₁ and 16,16-dimethyl-PGA₂-methyl ester) were found to block the proliferation of HTLV-1 infected cord blood lymphocytes (CBL) in vitro, thus preventing the clonal immortalisation that is considered as a predisposing condition to HTLV-1 positive leukaemia. PGA₁ and di-M-PGA₂ did not affect the long-term survival of normal non-infected CBL, whereas they suppressed the proliferation of an established cord-blood derived HTLV-1 positive cell line, MT-2. As shown by the number of HTLV-1 infected p19+ cells, the block of the selection of immortalised, infected clones by PGAs did not appear to be due to an inhibition of early stages of HTLV-1 infection. The possibility that the effect of PGAs could be mediated by an action of the immune response was also examined. PGAs regulated the cell-mediated cytotoxic function of CBL to a different extent when normal non-infected or HTLV-1 exposed CBL were compared. In fact, PGAs down-regulated the natural killing and macrophage/lymphocyte cytotoxic response of normal CBL, whereas they did not modify the already depressed immune response of CBL challenged with HTLV-1. These results suggest that the protective effect of PGAs against HTLV-1 infection in vitro is mostly related to the direct suppression of the clonal expansion of virus-infected cells, rather than to the anti-viral activity or modulation of the cell-mediated immunity.