Selection of HTLV-I 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-I infected cord blood lymphocytes (CBL) in vitro, thus preventing the clonal immortalisation that is considered as a predisposing condition to HTLV-I 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-I positive cell line, MT-2. As shown by the number of HTLV-I 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-I infection. The possibility that the effect of PGAs could be mediated by an action on 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-I 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-I. These results suggest that the protective effect of PGAs against HTLV-I 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.
D'Onofrio
C
C
Department of Experimental Medicine and Biochemical Sciences, II University of Rome, Italy.
Alvino
E
E
Garaci
E
E
Bonmassar
E
E
Santoro
M G
MG
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005312:Fetal Blood / Q000382:microbiology; D015490:HTLV-I Infections / Q000097:blood*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D008938:Mitosis / Q000187:drug effects; D011454:Prostaglandins A / Q000494:pharmacology*; D011455:Prostaglandins A, Synthetic / Q000494:pharmacology; D013997:Time Factors
D011454:Prostaglandins A; D011455:Prostaglandins A, Synthetic