For the large array of self-peptide/MHC class II (pMHC-II) complexes displayed in the body, it is unclear whether CD4+ T cell tolerance must be imparted for each individual complex or whether pMHC-II-nonspecific bystander mechanisms are sufficient to confer tolerance by acting broadly on T cells reactive to multiple self-pMHC-II ligands. Here, via reconstitution of T cell-deficient mice, we demonstrate that altered T cell selection on a single prostate-specific self-pMHC-II ligand renders recipient mice susceptible to prostate-specific T cell infiltration. Mechanistically, this self-pMHC-II complex is required for directing antigen-specific cells into the Foxp3+ regulatory T cell lineage but does not induce clonal deletion to a measurable extent. Thus, our data demonstrate that polyclonal T reg cells are unable to functionally compensate for a breach in tolerance to a single self-pMHC-II complex in this setting, revealing vulnerabilities in antigen-nonspecific bystander mechanisms of immune tolerance.Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1- memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1- cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality. Government motor vehicle crash reports used in the study of driver safety can be biased and incomplete. Naturalistic driving methods using in-vehicle instrumentation have been developed in recent years to objectively measure crashes and near crashes as they occur on the road using video and vehicle kinematic data. To examine visual risk factors associated with at-fault crashes and near crashes among older drivers, most of whom have age-related eye conditions associated with vision impairment. This prospective cohort study was conducted at an academic ophthalmology clinic from January 1, 2015, to November 10, 2018, among 154 adults 70 years of age or older who were legally licensed in Alabama and who reported currently driving at least 4 days per week; 137 of 151 participants (90.7%) had an age-related eye condition in at least 1 eye. Drivers participated in a baseline visual function assessment followed by installation of a data acquisition system recording multichannel synchronized video and vehicle kirashes and near crashes involving older drivers are objectively measured as they occur on the road, associations have been identified between impaired contrast sensitivity, slowed visual processing speed, and impaired motion perception and an increased rate of a combined total of at-fault crashes and near crashes.With the use of naturalistic driving methods in which crashes and near crashes involving older drivers are objectively measured as they occur on the road, associations have been identified between impaired contrast sensitivity, slowed visual processing speed, and impaired motion perception and an increased rate of a combined total of at-fault crashes and near crashes. While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year-long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. Crew members were tested before, during, and up to 1 year after spaceflight. This study compares ocular changes (peripapillary retinal edema, axial length, anteriorbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted. The COVID-19 pandemic led to sharp declines in cancer screening. However, the total deficit in screening in the US associated with the pandemic and the differential impact on individuals in different geographic regions and by socioeconomic status (SES) index have yet to be fully characterized. To quantify the screening rates for breast, colorectal, and prostate cancers associated with the COVID-19 pandemic in different geographic regions and for individuals in different SES index quartiles and estimate the overall cancer screening deficit in 2020 across the US population. This retrospective cohort study uses the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information covering approximately 60 million people in Medicare Advantage and commercial health plans from across geographically diverse regions of the US. Participants were individuals in the database in January through July of 2018, 2019, and 2020 without diagnosis of the cancer of including increased use of screening modalities that do not require a procedure. The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. TP0427736 Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Maternal test positivity for SARS-CoV-2 in pregnancy. In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2.