HTLV-1 Proliferation after CD8 + Cell Depletion by Monoclonal Anti-CD8 Antibody Administration in Latently HTLV-1-Infected Cynomolgus Macaques.

Human T-cell leukemia virus type 1 (HTLV-1) induces chronic asymptomatic latent infection with a substantial proviral load but without significant viral replication . Cumulative studies have indicated involvement of CD8-positive (CD8) cells, including virus-specific CD8 T cells in the control of HTLV-1 replication. However, whether HTLV-1 expression from latently infected cells occurs in the absence of CD8 cells remains unclear. Here, we examined the impact of CD8 cell depletion by monoclonal anti-CD8 antibody administration on proviral load in HTLV-1-infected cynomolgus macaques. Five cynomolgus macaques were infected with HTLV-1 by inoculation with HTLV-1-producing cells. Administration of monoclonal anti-CD8 antibody in the chronic phase resulted in complete depletion of peripheral CD8 T cells for approximately 2 months. All five macaques showed an increase in proviral load following CD8 cell depletion, which peaked just before the reappearance of peripheral CD8 T cells. Tax-specific CD8 T-cell responses were detected in these recovered CD8 T cells. Importantly, anti-HTLV-1 antibodies also increased after CD8 cell depletion, indicating HTLV-1 antigen expression. These results provide evidence indicating that HTLV-1 can proliferate from the latent phase in the absence of CD8 cells and suggest that CD8 cells are responsible for the control of HTLV-1 replication. HTLV-1 can cause serious diseases such as adult T-cell leukemia (ATL) in humans after chronic asymptomatic latent infection with substantial proviral load. Proviruses are detectable in peripheral lymphocytes in HTLV-1 carriers, and the association of a higher proviral load with a higher risk of disease progression has been observed. However, neither substantial viral structural protein expression nor viral replication was detectable . Cumulative studies have indicated involvement of CD8 cells, including virus-specific CD8 T cells in the control of HTLV-1 replication. In the present study, we showed that CD8 cell depletion by monoclonal anti-CD8 antibody administration results in HTLV-1 expression and an increase in proviral load in HTLV-1-infected cynomolgus macaques. Our results indicate that HTLV-1 can proliferate in the absence of CD8 cells, suggesting that CD8 cells are responsible for the control of HTLV-1 replication. This study provides insights into the mechanism of virus-host immune interaction in latent HTLV-1 infection.