Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging.

T cell polyfunctionality is a hallmark of protective immunity against pathogens and cancer, yet the molecular mechanism governing it remains mostly elusive. We found that canonical Wnt agonists inhibited human memory CD8 + T cell differentiation while simultaneously promoting the generation of highly polyfunctional cells. Downstream effects of Wnt activation persisted after removal of the drug, and T cells remained polyfunctional following subsequent cell division, indicating the effect is epigenetically regulated. Wnt activation induced a gene expression pattern that is enriched with stem cell–specific gene signatures and upregulation of protein arginine methyltransferase 1 (PRMT1), a known epigenetic regulator. PRMT1 + CD8 + T cells are associated with enhanced polyfunctionality, especially the ability to produce IL-2. In contrast, inhibition of PRMT1 ameliorated the effects of Wnt on polyfunctionality. Chromatin immunoprecipitation revealed that H4R3me2a, a permissive transcription marker mediated by PRMT1, increased at the IL-2 promoter loci following Wnt activation. In vivo, Wnt-treated T cells exhibited superior polyfunctionality and persistence. When applied to cytomegalovirus (CMV) donor–seropositive, recipient-seronegative patients (D+/R–) lung transplant patient samples, Wnt activation enhanced CMV-specific T cell polyfunctionality, which is important in controlling CMV diseases. These findings reveal a molecular mechanism governing T cell polyfunctionality and identify PRMT1 as a potential target for T cell immunotherapy.

Accurate 3D measuring systems thrive in the past few years. Most of them are based on laser scanners because these laser scanners are able to acquire 3D information directly and precisely in real time. However, comparing to the conventional cameras, these kinds of equipment are usually expensive and they are not commonly available to customers. Moreover, laser scanners interfere easily with each other sensors of the same type. On the other hand, computer vision-based 3D measuring techniques use stereo matching to acquire the cameras' relative position and then estimate the 3D location of points on the image. Because this kind of systems needs additional estimation of the 3D information, systems with real time capability often relies on heavy parallelism that prevents implementation on mobile devices. Inspired by the structure from motion systems, we propose a system that reconstructs sparse feature points to a 3D point cloud using a mono video sequence so as to achieve higher computation efficiency. The system keeps tracking all detected feature points and calculates both the amount of these feature points and their moving distances. We only use the key frames to estimate the current position of the camera in order to reduce the computation load and the noise interference on the system. Furthermore, for the sake of avoiding duplicate 3D points, the system reconstructs the 2D point only when the point shifts out of the boundary of a camera. In our experiments, we show that our system is able to be implemented on tablets and can achieve state-of-the-art accuracy with a denser point cloud with high speed.

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