Potential immunogenicity of adult T cell leukemia cells in vivo

Abstract

Experimental vaccines targeting human T cell leukemia virus type‐I (HTLV‐I) Tax have been demonstrated in a rat model of HTLV‐I‐induced lymphomas. However, the scarcity of HTLV‐I‐expression and the presence of defective HTLV‐I‐proviruses in adult T cell leukemia (ATL) cells have raised controversy about the therapeutic potential of HTLV‐I‐targeted immunotherapy in humans. We investigated the expression of HTLV‐I antigens in fresh ATL cells by using both in vitro and in vivo assays. In flow cytometric analysis, we found that 3 of 5 acute‐type and six of fifteen chronic‐type ATL patients tested showed significant induction of HTLV‐I Tax and Gag in their ATL cells in a 1‐day culture. Concomitantly with HTLV‐I‐expression, these ATL cells expressed co‐stimulatory molecules such as CD80, CD86 and OX40, and showed elevated levels of antigenicity against allogeneic T cells and HTLV‐I Tax‐specific cytotoxic T‐lymphocytes (CTL). Representative CTL epitopes restricted by HLA‐A2 or A24 were conserved in 4 of 5 acute‐type ATL patients tested. Furthermore, spleen T cells from rats, which had been subcutaneously inoculated with formalin‐fixed uncultured ATL cells, exhibited a strong interferon gamma‐producing helper T cell responses specific for HTLV‐I Tax‐expressing cells. Our study indicated that ATL cells from about half the patients tested readily express HTLV‐I antigens including Tax in vitro, and that ATL cells express sufficient amounts of Tax or Tax‐induced antigens to evoke specific T cell responses in vivo. © 2004 Wiley‐Liss, Inc.