Approximately one-tenth of the 10 million individuals living with human T-cell leukemia virus type-1 (HTLV-1) worldwide live in Japan. Most of these infected individuals live in the southwest region of Japan, including Okinawa prefecture; however, currently no prophylactic vaccine against HTLV-1 infection is available. For preventing the HTLV-1 spread, we previously generated a humanized monoclonal antibody (hu-LAT-27) that mediates both neutralization and antibody-dependent cellular cytotoxicity (ADCC). The neutralization epitope of LAT-27 is a linear amino acid sequence from residue 191 to 196 (Leu-Pro-His-Ser-Asn-Leu) of the HTLV-1 envelope gp46 protein. Here, we found that the LAT-27 epitope is well conserved among HTLV-1 clinical isolates prevalent in Okinawa. The hu-LAT-27 treatment inhibited syncytium formation by these clinical HTLV-1 isolates. Although an amino acid substitution at residue 192 in the LAT-27 epitope from proline to serine was found in a few HTLV-1 isolates, hu-LAT-27 could still react with a synthetic peptide carrying this amino acid substitution. These findings demonstrate the wide spectrum of hu-LAT-27 reactivity, suggesting that hu-LAT-27 may be a candidate drug for prophylactic passive immunization against HTLV-1 infection.

Since forkhead box P3 (FOXP3) is a hallmark of regulatory T (Treg) cells, the expansion of FOXP3⁺ adult T-cell leukemia/lymphoma (ATL) cells is believed to contribute to immune suppression and the pathogenesis of ATL. However, the mechanisms underlying the expansion of FOXP3⁺ ATL cells remain unclear. OX40, a co-stimulatory molecule, is expressed in ATL cells, and OX40 signaling has been shown to promote the differentiation and proliferation of Treg cells in mouse models. To investigate the mechanisms driving the expansion of FOXP3⁺ ATL cells, we examined the expression of OX40 and its ligand, OX40L. Our findings revealed that OX40 expression was elevated in patients with ATL and with a high frequency of FOXP3⁺ ATL cells. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) from patients with acute ATL cultured for 18 h demonstrated that FOXP3⁻ and FOXP3⁺ cells predominantly expressed OX40L and OX40, respectively. Furthermore, small interfering RNA-mediated FOXP3 knockdown in HTLV-1-infected cell lines increased OX40L expression. These results suggest that interactions between FOXP3⁻ OX40L⁺ cells and FOXP3⁺ OX40⁺ cells may promote the proliferation of FOXP3⁺ ATL cells.