title: Elimination of human T cell leukemia virus type-1-infected cells by neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies against human t cell leukemia virus type-1 envelope gp46.
abstract: Human T cell leukemia virus type-1 (HTLV-1) is prevalent worldwide with foci of high prevalence. However, to date no effective vaccine or drug against HTLV-1 infection has been developed. In efforts to define the role of antibodies in the control of HTLV-1 infection, we capitalized on the use of our previously defined anti-gp46 neutralizing monoclonal antibody (mAb) (clone LAT-27) and high titers of human anti-HTLV-1 IgG purified from HAM/TSP patients (HAM-IgG). LAT-27 and HAM-IgG completely blocked syncytium formation and T cell immortalization mediated by HTLV-1 in vitro. The addition of these antibodies to cultures of CD8(+) T cell-depleted peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients at the initiation of culture not only decreased the numbers of Tax-expressing cells and the production of HTLV-1 p24 but also inhibited the spontaneous immortalization of T cells. Coculture of in vitro-HTLV-1-immortalized T cell lines with autologous PBMCs in the presence of LAT-27 or HAM-IgG, but not an F(ab')2 fragment of LAT-27 or nonneutralizing anti-gp46 mAbs, resulted in depletion of HTLV-1-infected cells. A 24-h (51)Cr release assay showed the presence of significant antibody-dependent cellular cytotoxicity (ADCC) activity in LAT-27 and HAM-IgG, but not F(ab')2 of LAT-27, resulting in the depletion of HTLV-1-infected T cells by autologous PBMCs. The depletion of natural killer (NK) cells from the effector PBMCs reduced this ADCC activity. Altogether, the present data demonstrate that the neutralizing and ADCC-inducing activities of anti-HTLV-1 antibodies are capable of reducing infection and eliminating HTLV-1-infected cells in the presence of autologous PBMCs.
authors: 1 Department of Immunology, Graduate School of Medicine, University of the Ryukyus , Okinawa, Japan .
authors: Yuetsu
authors: Y
authors: Tanaka
authors: Yoshiaki
authors: Y
authors: Takahashi
authors: Reiko
authors: R
authors: Tanaka
authors: Akira
authors: A
authors: Kodama
authors: Hideki
authors: H
authors: Fujii
authors: Atsuhiko
authors: A
authors: Hasegawa
authors: Mari
authors: M
authors: Kannagi
authors: Aftab A
authors: AA
authors: Ansari
authors: Mineki
authors: M
authors: Saito
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002470:Cell Survival; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G