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

Yuetsu Tanaka, Yoshiaki Takahashi, Reiko Tanaka, Akira Kodama, Hideki Fujii, Atsuhiko Hasegawa, Mari Kannagi, Aftab A. Ansari, Mineki Saito

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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 51Cr 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.

Original languageEnglish
Pages (from-to)542-552
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume30
Issue number6
DOIs
Publication statusPublished - 2014 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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