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T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4+ and CD8+ T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4+ and CD8+ T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8+ T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.

Photosynthetic microorganisms typically have multiple isoforms of the electron transfer protein ferredoxin, although we know little about their exact functions. Surprisingly, a Chlamydomonas reinhardtii mutant null for the ferredoxin-5 gene (FDX5) completely ceased growth in the dark, with both photosynthetic and respiratory functions severely compromised; growth in the light was unaffected. Thylakoid membranes in dark-maintained fdx5 mutant cells became severely disorganized concomitant with a marked decrease in the ratio of monogalactosyldiacylglycerol to digalactosyldiacylglycerol, major lipids in photosynthetic membranes, and the accumulation of triacylglycerol. Furthermore, FDX5 was shown to physically interact with the fatty acid desaturases CrΔ4FAD and CrFAD6, likely donating electrons for the desaturation of fatty acids that stabilize monogalactosyldiacylglycerol. Our results suggest that in photosynthetic organisms, specific redox reactions sustain dark metabolism, with little impact on daytime growth, likely reflecting the tailoring of electron carriers to unique intracellular metabolic circuits under these two very distinct redox conditions.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103+ resident MAIT cells presented an immunoregulatory CD39highCD27low profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39high and hepatic CD56+ adaptations accumulated with donor age. CD56+ MAIT cells displayed limited T cell receptor–repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures. Editor's summary: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial riboflavin pathway–derived metabolites. Our understanding of MAIT cell functions in tissue homeostasis and antimicrobial responses has primarily relied on studies of mice and human peripheral blood. Using paired samples from adult human blood and mucosal and lymphoid tissues, Kammann et al. performed a cross-tissue characterization of human MAIT cells. Tissue-specific adaptations included a population of intestinal CD39hi MAIT cells with an immunoregulatory phenotype and liver-enriched CD56+ MAIT cells bearing enhanced effector capacity and innate-like features. Together, these findings highlight the phenotypic and functional specialization of human MAIT cells within specific tissue sites. —Claire Olingy [ABSTRACT FROM AUTHOR]

Tissue-resident memory CD8+ T cells serve as a first-line defense against many pathogens. In this issue of Immunity , Buquicchio et al. unveil the epigenomic landscapes of virus-specific CD8+ T cell subsets, highlighting common and organ-specific regulators driving their differentiation. [ABSTRACT FROM AUTHOR]

Among the issues on which health directions focus, fall risk is one of major importance since it affects patients hospitalized in both acute and rehabilitative hospitals. In this context, few publications have proposed a managerial approach aimed at (a) investigating several factors related to falls and (b) trying to acquire more knowledge and comprehension when analyzing the data collected. Consequently, this paper pursues such objectives by investigating data related to falls (and the recurrence of falls) registered in a rehabilitation hospital within the years 2020 and 2021. A multidisciplinary team (clinical staff and engineers) registered 238 first falls, and descriptive statistics were used to analyze the fall-related anamnestic and clinical data. Then, appropriate statistical analyses were used to compare the same data—this time distinguishing fallers/recurrent fallers—and, again, descriptive statistics were used to analyze the consequences of falls. The statistical analyses allowed us to gain insights into the fall mechanisms, the main places in which falls took place, the impacts of drugs, and fall consequences (e.g., the potential extra costs for the hospital). Moreover, the Morse and Stratify risk tools, state of consciousness, and fall containment measures were proven to be statistically significant features for distinguishing fallers and recurrent fallers, and they may be further investigated to define more accurate preventive measures within rehabilitation hospitals. [ABSTRACT FROM AUTHOR]