HBV-specific CD8 T cells quantity is not proportional to the
extend of liver damage. (实事, 不与主流观点有冲突。这点也不能支持谁是凶手的结论)
Hepatic flares are likely a result of complex and still undetermined
interactions between innate and adaptive immune mechanisms
within the liver.
The prevailing idea is that the hepatic flares are the result of a
quantitative recovery of HBV-specific T cell response.
(他们理解错了主流吧,我看了论文也不少,主流是这样认识的吗?骆老的理论也属主流,CD4+T CELL 不会导致肝损伤,而主流是肝损伤是CD8+T CELL 应答、巨噬细胞、NK的结果。)
These acute exacerbations of liver damage (called hepatic
flares, HF) can occur spontaneously, be induced by IFN-a therapy or by
the withdrawal of treatment with nucleoside analogues [2]. They are often
preceded by high levels of HBV replication and by progressive accumulation
of HBV antigens [3] and are characterized by an increase liver
pathological activity (manifested as an increase in the level of ALT).
However, there are scarce experimental evidences to support such a
scenario, which are limited to data showing [5] an increment on
CD4+ T cell proliferation against the whole HBcAg around the time
of hepatic flares
(CD4+ T cell 非肝损伤机制清除HBV,分泌伽马干扰素,共识了)
Moreover, two other important points need to be taken in account: the
first is that the frequency of circulating and intrahepatic HBV-specific
CD8+ cells in patients with chronic HBV infection correlate with
HBV control and not with liver damage.
(这点不奇怪,很正常。不与主流冲突。只是主流未认清CD8+ cells的性质,并不能证明CD8+ cells永远不会导致肝损伤)
Secondly, work in animal
models has clearly shown that the bulk of liver damage is not direCD8+ cellsy
cause by HBV-specific CD8+ cells, but is mainly caused by their
ability to trigger a series of secondary events including hepatic
granulocyte infiltration, chemokine production and subsequent
recruitment of an inflammatory infiltrate composed of macrophages,
NK cells and T cells
(不奇怪,不能推翻免疫治病论。只是讨论在此情况、此环境下,谁是凶手的问题。环境不同,另当别论)
CTL有很积极的一面,我当时只是认为是 有是有非,如果能证实在人体内的HBV引起的严重肝损失与CTL无关,只是天然免疫的结果,那是好事,是有是无非了。但是,a干扰素的作用原理是什么?被认为是扩增DC,适应免疫的应答,也就是扩增一个T细胞应答。a干扰素会引起肝损伤加剧,那么就是干扰素后的CTL攻击导致肝损伤。此推论有何疑问呢?
As a consequence, there is no direct
correlation between HBV-specific CD8+ cells frequency and the extent of
liver damage, and hepatic flares cannot be simply associated with an
increment of the HBV-specific T cell response
(其关系恐怕是他们未发现而已,除非他们证实,大量病例,任何情况,在人体的严重肝损伤与CD8+ cells无关)。
与主流区别不大,只是在复杂的免疫应答中,争论谁是主要凶手罢了。作者: hundun 时间: 2010-5-31 20:51