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When considering that virus persistence enhances T cell agin
When considering that virus persistence enhances T cell aging, it is notable that NRON has been found to modulate HIV latency by both NFAT-dependent (Imam et al., 2015) and NFAT-independent (Li et al., 2016) mechanisms. It is also intriguing that episodic reactivation of HIV latency is similarly accompanied by an expansion of CD28nullCD8+T LXR-623 sale (Borthwick et al., 1994), which has led to HIV persistence being considered as an model of accelerated immunity aging [reviewed by (Desai and Landay, 2010)]. Similar to elderly “silent” CMV carriers, the increasing number of elderly HIV subclinical carriers also present the dilemma of age-accumulated virus contributions during CD8+ T cell aging [reviewed by (Pathai et al., 2014)]. Interestingly, CMV-specific CD8+ T cells often exceed HIV-specific CD8+ T cells in these subclinical HIV carriers who are virtually always CMV co-carriers (Effros, 2016)]. These results support the idea that NRON is substantially involved in the process of extrinsic viruses repetitively enhancing age-accumulated T cell aging.
Our study had two main shortcomings. First, the subclinical hallmarks of CMV carriers at very advanced age only represent a relatively small portion of the elderly population, because the majority of nonagenarians cannot be free from clinical manifestations in the long-term. Second, we obtained only one candidate lncRNA as an integrative biomarker, after our validation series. These issues are both reflections of the complexity of age-accumulated CMV-enhanced CD8+ T cell aging. We attempted to validate the expression of NRON in other episodes of CMV to HLA-restricted TCRs rather than CMVpp65-HLA-0201*; however, this might require single-cell techniques in our advanced-age cohort.
In conclusion, reduced expression of the lncRNA NRON is a potential subclinical biomarker for age-accumulated CMV-enhanced CD8+ T cell aging. NRON-dependent regulation of CMV-involved T cell aging warrants further exploration.
The following are the supplementary data related to this article.
Funding
This work was supported by the National Natural Science Foundation of China (Grant number: 81671383); Natural Science Foundation of Heilongjiang Province (Grant number: C201245); Fund of First Hospital of Harbin Medical University (Grant number: 2017Y008).