艾滋病病毒入侵后,，人體免疫細(xì)胞的功能會受到削弱，科學(xué)家最近發(fā)現(xiàn)了其中的機(jī)理,。這一發(fā)現(xiàn)將有助于人們找到治療艾滋病的新方法,。
據(jù)最新一期英國《自然·醫(yī)學(xué)》雜志報道，美國波士頓馬薩諸塞綜合醫(yī)院的一個研究小組對南非71名未接受過治療的艾滋病患者的“CD8”免疫細(xì)胞進(jìn)行檢測后發(fā)現(xiàn),，病人體內(nèi)艾滋病病毒越多,，“CD8”表面上一種名為“PD-1”的受體越多。但當(dāng)研究人員給病人服用抗逆轉(zhuǎn)錄病毒藥物以大量抑制病人血液中的病毒數(shù)量后,，病人“CD8”細(xì)胞表面的“PD-1”受體數(shù)量也隨之減少,。
研究人員解釋說，艾滋病病毒增加,，會使免疫細(xì)胞“CD8”開始大量產(chǎn)生“PD-1”受體,。隨著這種受體在免疫細(xì)胞表面堆積，免疫細(xì)胞功能變?nèi)?，只能產(chǎn)生很少的化學(xué)物質(zhì)來殺死病毒,。
加拿大蒙特利爾中心醫(yī)院的一個研究小組對19名北美病人的研究也得出了同樣的結(jié)果。
據(jù)報道,，兩個研究小組都成功利用“PD-1”受體的抗體,，以幫助免疫細(xì)胞“CD8”恢復(fù)正常功能。在實(shí)驗(yàn)過程中,，經(jīng)過處理的免疫細(xì)胞“CD8”恢復(fù)了正?；盍Γa(chǎn)出了可以攻擊艾滋病病毒的γ干擾素等化學(xué)物質(zhì),。研究人員目前在實(shí)驗(yàn)鼠身上已經(jīng)證明了這一方法的有效性,，希望下一步能盡快進(jìn)行人體實(shí)驗(yàn)。
部分英文原文：
Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L2, inhibits proliferation and cytokine production mediated by antibodies to CD3 . Blocking the PD-1–PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8+ T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load8. During chronic HIV infection, HIV-specific CD8+ T cells are functionally impaired, showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate. Here, we found that PD-1 was upregulated on HIV-specific CD8+ T cells; PD-1 expression levels were significantly correlated both with viral load and with the reduced capacity for cytokine production and proliferation of HIV-specific CD8+ T cells. Notably, cytomegalovirus (CMV)-specific CD8+ T cells from the same donors did not upregulate PD-1 and maintained the production of high levels of cytokines. Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen. The accumulation of HIV-specific dysfunctional CD8+ T cells in the infected host could prevent the renewal of a functionally competent HIV-specific CD8+ repertoire.
