- 作者: Mingjie Zhang Xingxiang Li Xiaowu Pang Linna Ding Owen Wood Kathlene Clouse Indira Hewlett Andrew I. Dayton
- 作者服務機構: Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Division of Monoclonal Antibodies, Office of Therapeutics Research and Review, Center for Biologics Evaluation and Research, FDA, Rockville, MD., USA
- 中文摘要: --
- 英文摘要: The induction of apoptosis in T cells by bystander cellshas been repeatedly implicated as a mechanism contrib-uting to the T cell depletion seen in HIV infection. It hasbeen shown that apoptosis could be induced in T cellsfrom asymptomatic HIV-infected individuals in a Fas-independent, TNF-related apoptosis-inducing ligand(TRAIL)-dependent manner if the cells were pretreatedwith anti-CD3. It has also been shown that T cells fromHIV-infected patients were even more sensitive to TRAILinduction of apoptosis than they were to Fas induction.Recently, it has been reported that in an HIV-1 SCID-Humodel, the vast majority of the T cell apoptosis is notassociated with p24 and is therefore produced by by-stancler effects. Furthermore, few apoptotic cells wereassociated with neighboring cells which were positivefor either Fas ligand or TNF. However, most of the apop-totic cells were associated with TRAIL-positive cells. Thenature of these TRAIL-positive cells was undetermined.Here, we report that HIV infection of primary humanmacrophages switches on abundant TRAIL productionboth at the RNA and protein levels. Furthermore, moremacrophages produce TRAIL than are infected by HIV,indicating that a bystander mechanism may, at least inpart, upregulate TRAIL. Exogenously supplied HIV-1 Tatprotein upregulatesTRAIL production by primary humanmacrophages to an extent indistinguishable from infec-tion. The results suggest a model in which HIV-1-infectedcells produce extracellular Tat protein, which in turnupregulates TRAIL in macrophages which then can in-duce apoptosis in bystander T cells.
- 中文關鍵字: --
- 英文關鍵字: HIV. Tat. TRAIL. Apoptosis. Macrophage