Search

Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells. [ABSTRACT FROM AUTHOR]

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)‐cells have recently gained much attention. We performed an in‐deep phenotypic analysis of NK‐cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty‐seven PLWH (22 long‐term EC [PLWH‐long‐term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH‐onART], and 10 noncontrollers cART‐naïve [PLWH‐offART]), and 20 uninfected controls were included. NK‐cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK‐cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK‐cells clusters based on the expression levels of the 15 different markers. PLWH‐offART presented the highest disturbance of NK‐cells homeostasis and this was not completely restored by long‐term ART. Interestingly, long term spontaneous control of HIV (PLWH‐LTEC group) was associated with a specific profile of NK‐cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p‐value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p‐value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long‐term control of HIV. [ABSTRACT FROM AUTHOR]

Human-adipose-derived mesenchymal stem cells (hADMSCs) are multipotent stem cells which have become of great interest in stem-cell therapy due to their less invasive isolation. However, they have limited migration and short lifespans. Therefore, understanding the mechanisms by which these cells could migrate is of critical importance for regenerative medicine. Methods: Looking for novel alternatives, herein, hADMSCs were isolated from adipose tissue and co-cultured with human monocytes ex vivo. Results: A new fused hybrid entity, a foam hybrid cell (FHC), which was CD90+CD14+, resulted from this co-culture and was observed to have enhanced motility, proliferation, immunomodulation properties, and maintained stemness features. Conclusions: Our study demonstrates the generation of a new hybrid cellular population that could provide migration advantages to MSCs, while at the same time maintaining stemness properties. [ABSTRACT FROM AUTHOR]

SCD25, sTim-3 and Galectin-9 showed to be increased in patients versus HV despite the fact that they developed mild disease (Figure 1C-E). We found sCD25, sTim-3, Galectin-9, sPD-L1 and sCD86 exhibited differences between groups (Figure 1C-L). In addition, sCD25, sTim-3, Galectin-9, sPD-L1 and sPD-1 showed increased levels in severe patients and/or exitus compared with mild ones (Figure 1C-G). GLO:F2H7/01oct21:ctm2573-fig-0001.jpg PHOTO (COLOR): 1 Distribution of patients and plasma immune checkpoint levels according to outcome of patients with COVID-19 on admission, compared with HVs. [Extracted from the article]

We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time. [Display omitted] • History of SARS-CoV-2 infection affects longitudinal responses to BNT162b2 vaccine • Lower humoral but enhanced cellular responses early after vaccine in naive subjects • Comparable humoral and cellular responses almost 8 months after vaccination • Similar S-specific B cells late after vaccine in those naive and recovered from COVID-19 Lozano-Rodríguez et al. show that naive subjects have enhanced SARS-CoV-2 spike-specific T reactions but reduced humoral-specific responses compared with individuals recovered from COVID-19. However, almost 8 months after vaccination, comparable specific responses are observed with equivalent levels of SARS-CoV-2-specific B cells and neutralizing antibodies. [ABSTRACT FROM AUTHOR]