In this commentary, we discuss the physiological effects of wearing masks for prolonged periods of time, including special considerations, such as mask wearing among those who engage in exercise training, and concerns for individuals with pre-existing chronic diseases. In healthy populations, wearing a mask does not appear to cause any harmful physiological alterations, and the potentially life-saving benefits of wearing face masks seem to outweigh the documented discomforts (e.g. headaches). However, there continues to be controversy over mask wearing in the United States, even though wearing a mask appears to have only minor physiological drawbacks. While there are minimal physiological impacts on wearing a mask, theoretical evidence suggests that there may be consequential psychological impacts of mask wearing on the basic psychological needs of competence, autonomy, and relatedness. These psychological impacts may contribute to the controversy associated with wearing masks during the COVID-19 pandemic in the United States. After we discuss the physiological impacts of mask wearing, we will discuss psychological effects associated with wearing masks during the COVID-19 pandemic.

T cell anergy is characterized by the inability of the T cell to produce IL-2 and proliferate. It is reversible by the addition of exogenous IL-2. A similar state of unresponsiveness is observed when the proliferative response of murine CD4+CD25− T cells is suppressed in vitro by coactivated CD4+CD25+ T cells. We have developed a suppression system that uses beads coated with anti-CD3 and anti-CD28 Abs as surrogate APCs to study the interaction of CD4+CD25+ and CD4+CD25− T cells in vitro. CD4+CD25+ T cell-induced suppression, in this model, was not abrogated by blocking the B7-CTLA-4 pathway. When the CD4+CD25− T cells were separated from the CD4+CD25+ suppressor cells after 24 h of coactivation by the Ab-coated beads, the CD4+CD25− T cells were unable to proliferate or to produce IL-2 upon restimulation. The induction of this anergic phenotype in the CD4+CD25− T cells correlated with the up-regulated expression of the gene related to anergy in lymphocytes (GRAIL), a novel anergy-related gene that acts as a negative regulator of IL-2 transcription. This system constitutes a novel mechanism of anergy induction in the presence of costimulation.

T cell anergy may serve to limit autoreactive T cell responses. We examined early changes in gene expression after antigen-TCR signaling in the presence (activation) or absence (anergy) of B7 costimulation. Induced expression of GRAIL (gene related to anergy in lymphocytes) was observed in anergic CD4(+) T cells. GRAIL is a type I transmembrane protein that localizes to the endocytic pathway and bears homology to RING zinc-finger proteins. Ubiquitination studies in vitro support GRAIL function as an E3 ubiquitin ligase. Expression of GRAIL in retrovirally transduced T cell hybridomas dramatically limits activation-induced IL-2 and IL-4 production. Additional studies suggest that GRAIL E3 ubiquitin ligase activity and intact endocytic trafficking are critical for cytokine transcriptional regulation. Expression of GRAIL after an anergizing stimulus may result in ubiquitin-mediated regulation of proteins essential for mitogenic cytokine expression, thus positioning GRAIL as a key player in the induction of the anergic phenotype.

CD154 expression is regulated throughout a time course of CD3-dependent T cell activation by differential mRNA decay. To understand the molecular basis of the “stability” phase of this pathway, experiments were conducted to identify sequences and specific complexes important in this regulation. Gel retardation assays using extracts from both Jurkat T cells and CD3-activated CD4+ T cells revealed a major complex (complex I) that bound a 65-bp highly CU-rich region of the CD154 3′ untranslated region. The specificity of the CU-rich element for complex-I formation was confirmed by disruption of this complex by oligo(dCT) competition. Formation of complex I strongly correlated with CD154 mRNA stability across a time course of T cell activation. UV cross-linking identified a major oligo(dCT)-sensitive species at ∼90 kDa that showed induced and increased expression in extracts from 24- and 48-hr anti-CD3-activated T cells, respectively. This protein was absent in equivalent extracts from resting or 2-h-activated T cells. Using an in vitro decay assay, we found that a CD154-specific transcript was more rapidly degraded in 2-h-activated extract and stabilized in the 24- and 48-h extracts compared to extracts from resting T cells. Disruption of complex I resulted in the rapid decay of a CD154-specific transcript demonstrating a functional role for complex I in mRNA stabilization in vitro. These studies support a model of posttranscriptional regulation of CD154 expression being controlled in part by the interaction of a poly(CU)-binding complex with a specific sequence in the 3′ untranslated region.

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