Inhibition of R5-tropic HIV type-1 replication in CD4⁺ natural killer T cells by γδ T lymphocytes.

After the development of highly active anti-retroviral therapy, it became clear that the majority of emergent HIV-1 is macrophage-tropic and infects CD4⁺, CCR5-expressing cells (R5-tropic). There are three distinct cell populations, R5-tropic, HIV-1-susceptible CD4⁺ cells: (i) natural killer T (NKT) cells, (ii) dendritic cells and macrophages, and (iii) tissue-associated T cells residing primarily at mucosal surfaces. We have confirmed that CD4⁺ NKT cells derived from peripheral blood mononuclear cells (PBMCs) predominantly express CCR5 rather than CXCR4, whereas the reverse is true for CD4⁺ T cells derived from circulating PBMCs, and that R5-tropic HIV-1 expands efficiently in the CD4⁺ NKT cells. Moreover, when PBMCs depleted of CD8α⁺ cells were stimulated in the presence of α-galactosylceramide (α-GalCer) and R5-tropic HIV-1 [NL(AD8)], the production of HIV-1 virions was not suppressed, whereas, similar to the untreated PBMCs, depletion of CD8ß⁺ cells from PBMCs significantly inhibited virion production. These findings suggest that CD8αα⁺ but not CD8αß⁺ cells may have the ability to inhibit R5-tropic HIV-1 replication in CD4⁺ NKT cells. Here, we show that co-culturing R5-tropic HIV-1-infected CD4⁺ NKT cells with CD8αα⁺ γδ T cells, in particular Vγ1Vδ1 cells, but not with CD8αα⁺ NKT cells or CD8αα⁺ dendritic cells, inhibits HIV-1 replication mainly by secreting chemokines, such as macrophage inflammatory proteins 1α and 1ß and RANTES. Collectively, these results indicate the importance of CD8αα⁺ γδ T cells in the control of R5-tropic HIV-1 replication and persistence in CD4⁺ NKT cells.

A case of migraine without aura that was successfully treated with an herbal medicine.

OBJECTIVE: Migraine is a common neurologic condition characterized by the disabling effects it has on the patient. Despite recent progress in drug development, better pharmacotherapies against migraine are still needed. This report describes an herbal medicine that has a strong pain-relieving effect against migraine. PATIENT: This case involved a 49-year-old woman with a 16-year history of headaches. Migraine without aura had been diagnosed at age 47 years. Despite taking antiepileptic drugs as prophylaxis, she had migraines almost three times a week, especially in the morning. As a result, 3 months before her visit to the study clinic she was prescribed sumatriptan, which she had to take for each attack. However, sumatriptan sometimes failed to work as a painkiller, and the patient did not want to continue taking it because she was worried about overuse. INTERVENTION AND OUTCOME: According to traditional Japanese (Kampo) and Chinese herbal medicine, the patient was prescribed an oral sanno-shashin-to (Xie Xin Tang) extract formula to take at night to prevent her migraines. Soon after she started taking the formula, the intensity of her morning headaches markedly decreased, to the extent that triptans were no longer needed. Furthermore, her residual headaches quickly disappeared after the additional administration of the formula in the morning. CONCLUSIONS: Sanno-shashin-to might have both prophylactic and therapeutic effects against migraine without aura. Although the underlying mechanism behind the effectiveness of this herbal medicine against migraine has not been fully elucidated, it is a possible option for the treatment of this type of headache.