SummaryAfter the development of highly active anti-retroviral therapy, it became clear that the majority of emergent HIV-1 is macrophage-tropic and infects CD4

Although HIV-1 can be successfully eradicated from the circulating blood of HIV-1-infected individuals using anti-retroviral therapy (ART), HIV-1 virions emerge immediately after the interruption of ART. This study was aimed to investigate the origin of the emerged HIV-1. After obtaining informed consent, blood samples from nine HIV-1-infected individuals and endoscopic ileum samples from five of the individuals were obtained. Purified peripheral mononuclear cells (PBMCs)and ileum cells were analyzed by flow-cytometry, and the V3 loop sequences of the HIV-1 envelope protein were determined. By comparing the V3 loop sequences of the samples, we confirmed that the provirus hidden in the CD4(+) PBMCs was not the source of the HIV-1 that emerged after the interruption of ART. Although free virus and HIV-1-p24 antigen (p24)-positive cells were not seen in the blood of patients receiving ART, proviral DNA and p24 could be detected in the ileum from the same patient. Among the HIV-1-infected CD4(+) cells in the ileum samples, Vα24(+) natural killer T (NKT) cells were the major p24-positive cells. These results suggest that the innate NKTcells in the mucosal compartment are the most likely candidates for the origin of the HIV-1 that emerged after ART was interrupted.

We established transfectants expressing T cell receptors (TCRs) either for Vγ1 and Vδ1 (1C116) or for Vγ2 and Vδ2 (2C21) using the TCR-deficient Jurkat T cell line J.RT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. Clone 2C21 was specifically stimulated by previously reported ligands for Vγ2Vδ2 (Vδ2)-TCR such as isopentenyl pyrophospate (IPP), ethylamine, or risedronate. In contrast, clone 1C116 was strongly stimulated through the Vγ1Vδ1 (Vδ1)-TCR by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring. Additionally, hesperidin and linarin showed stimulatory activity for peripheral blood mononuclear cell (PBMC)-derived T cells expressing Vδ1-TCR; these activated Vδ1 + T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. Such PBMC-derived Vδ1 + T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in CD4 + NKT cells in a dose-dependent manner. To the best of our knowledge, this is the first demonstration that flavonoid glycosides activate functional Vδ1 + T cells.

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Histiocytic sarcoma (HS) is a rare malignancy of soft tissues with an unknown etiology. The CHOP (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride and prednisolone) regimen is often adopted as first-line chemotherapy; however, its therapeutic efficacy against HS is usually low. We herein first present the case of a patient with HS who was infected with human immunodeficiency virus-1 (HIV) in whom treatment with a combination of CHOP and antiretroviral therapy (ART) was successful. The patient has been in complete remission for 12 months following the discontinuation of chemotherapy under continuous ART. This case report may help to promote further investigation of both HS and HIV-related malignancy.