Potential immunogenicity of adult T cell leukemia cells in vivo.
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.
Kurihara
Kiyoshi
K
Department of Immunotherapeutics, Medical Research Division, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Harashima
Nanae
N
Hanabuchi
Shino
S
Masuda
Masato
M
Utsunomiya
Atae
A
Tanosaki
Ryuji
R
Tomonaga
Masao
M
Ohashi
Takashi
T
Hasegawa
Atsuhiko
A
Masuda
Takao
T
Okamura
Jun
J
Tanaka
Yuetsu
Y
Kannagi
Mari
M
D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007564:Japan; D015461:Leukemia, Prolymphocytic, T-Cell / Q000473:pathology / Q000821:virology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D014183:Transplantation, Heterologous / Q000473:pathology
D017931:DNA Primers