The role of neuroimaging in the determination of brain death.

Brain death is the irreversible cessation of all brain function. Although protocols for its determination vary among countries, the concept of brain death is widely accepted, despite ethical and religious issues. The pathophysiology of brain death is related to hypoxia and ischemia in the setting of extensive brain injury. It is also related to the effects of brain edema, which increases intracranial pressure, leading to cerebral circulatory arrest. Although the diagnosis of brain death is based on clinical parameters, the use of neuroimaging to demonstrate diffuse brain injury as the cause of coma prior to definitive clinical examination is a prerequisite. Brain computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate diffuse edema, as well as ventricular and sulcal effacement, together with brain herniation. Angiography (by CT or MRI) demonstrates the absence of intracranial arterial and venous flow. In some countries, electroencephalography, cerebral digital subtraction angiography, transcranial Doppler ultrasound, or scintigraphy/single-photon emission CT are currently used for the definitive diagnosis of brain death. Although the definition of brain death relies on clinical features, radiologists could play an important role in the early recognition of global hypoxic-ischemic injury and the absence of cerebral vascular perfusion.

A morte encefálica é a cessação irreversível de todas as funções cerebrais. Embora os protocolos para sua determinação variem entre os países, o conceito de morte encefálica é amplamente aceito, apesar de questões éticas e religiosas. A fisiopatologia da morte encefálica está relacionada a hipóxia e isquemia no cenário de uma lesão cerebral difusa. Também está relacionada aos efeitos do edema cerebral, que aumenta a pressão intracraniana, levando à parada da circulação cerebral. Embora o diagnóstico de morte encefálica seja baseado em parâmetros clínicos, o uso de neuroimagem para demonstrar lesão cerebral difusa como causa do coma antes do exame clínico definitivo é um pré-requisito. A tomografia computadorizada (TC) e a ressonância magnética (RM) de crânio demonstram edema difuso e apagamento de ventrículos e sulcos, associados a herniações transcompartimentais. A angio-TC e a angio-RM demonstram a ausência de fluxo arterial e venoso intracraniano. Em alguns países, a eletroencefalografia, a angiografia por subtração digital cerebral, a ultrassonografia transcraniana com Doppler ou a cintilografia/TC por emissão de fóton único são atualmente usadas para o diagnóstico definitivo de morte encefálica. Embora a definição de morte encefálica dependa de características clínicas, os radiologistas podem desempenhar papel importante no reconhecimento precoce da lesão hipóxico-isquêmica global e da ausência de perfusão vascular cerebral.

COVID-19 associated with encephalomyeloradiculitis and positive anti-aquaporin-4 antibodies: Cause or coincidence?

Neurologic complications are being recognized as important outcomes of coronavirus disease 2019 (COVID-19). Pathogenesis is varied and incompletely understood, and may include neuroinvasion, indirect post-infectious neuroinflammation, and cerebrovascular pathologies. We present a case of COVID-19-related encephalomyeloradiculitis with clinical and magnetic resonance imaging characteristics of neuromyelitis optica spectrum disorders that was associated with anti-aquaporin-4 antibodies. Our case suggests post-infectious autoimmunity as a mechanism in at least a subset of patients with COVID-19-related neurologic disease.

Intrauterine IPEX.

IPEX is one of the few Inborn Errors of Immunity that may manifest in the fetal period, and its intrauterine forms certainly represent the earliest human autoimmune diseases. Here, we review the clinical, histopathologic, and genetic findings from 21 individuals in 11 unrelated families, with nine different mutations, described as cases of intrauterine IPEX. Recurrent male fetal death (multigenerational in five families) due to hydrops in the midsemester of pregnancy was the commonest presentation (13/21). Noteworthy, in the affected families, there were only fetal- or perinatal-onset cases, with no affected individuals presenting milder forms with later-life manifestation. Most alive births were preterm (5/6). Skin desquamation and intrauterine growth restriction were observed in part of the cases. Fetal ultrasonography showed hyperechoic bowel or dilated bowel loops in the five cases with available imaging data. Histopathology showed multi-visceral infiltrates with T lymphocytes and other cells, including eosinophils, the pancreas being affected in most of the cases (11/21) and as early as at 18 weeks of gestational age. Regarding the nine FOXP3 mutations found in these cases, six determine protein truncation and three predictably impair protein function. Having found distinct presentations for the same FOXP3 mutation in different families, we resorted to the mouse system and showed that the scurfy mutation also shows divergent severity of phenotype and age of death in C57BL/6 and BALB/c backgrounds. We also reviewed age-of-onset data from other monogenic Tregopathies leading to IPEX-like phenotypes. In monogenic IPEX-like syndromes, the intrauterine onset was only observed in two kindreds with IL2RB mutations, with two stillbirths and two premature neonates who did not survive. In conclusion, intrauterine IPEX cases seem to constitute a particular IPEX subgroup, certainly with the most severe clinical presentation, although no strict mutation-phenotype correlations could be drawn for these cases.

Global Fit to Modified Neutrino Couplings and the Cabibbo-Angle Anomaly.

Recently, discrepancies of up to 4σ between the different determinations of the Cabibbo angle were observed. In this context, we point out that this "Cabibbo-angle anomaly" can be explained by lepton flavor universality violating new physics in the neutrino sector. However, modified neutrino couplings to standard model gauge bosons also affect many other observables sensitive to lepton flavor universality violation, which have to be taken into account in order to assess the viability of this explanation. Therefore, we perform a model-independent global analysis in a Bayesian approach and find that the tension in the Cabibbo angle is significantly reduced, while the agreement with other data is also mostly improved. In fact, nonzero modifications of electron and muon neutrino couplings are preferred at more than 99.99% C.L. (corresponding to more than 4σ). Still, since constructive effects in the muon sector are necessary, simple models with right-handed neutrinos (whose global fit we update as a by-product) cannot fully explain data, pointing towards more sophisticated new physics models.

TLR9 Signaling Suppresses the Canonical Plasma Cell Differentiation Program in Follicular B Cells.

The relative potency and quality of mouse B cell response to Toll-like receptors (TLRs) signaling varies significantly depending on the B cell subset and on the TLR member being engaged. Although it has been shown that marginal zone cells respond faster than follicular (FO) splenic B cells to TLR4 stimulus, FO B cells retain full capacity to proliferate and generate plasmablasts and plasma cells (PBs/PCs) with 2-3 days delayed kinetics. It is not clear whether this scenario could be extended to other members of the TLR family. Here, using quantitative cell culture conditions optimized for B cell growth and differentiation, we show that TLR9 signaling by CpG, while promoting vigorous proliferation, completely fails to induce differentiation of FO B cells into PBs/PCs. Little or absent Ig secretion following TLR9 stimulus was accompanied by lack of expression of cell surface markers and canonical transcription factors involved in PB/PC differentiation. Moreover, not only TLR9 did not induce plasmocyte differentiation, but it also strongly inhibited the massive PB/PC differentiation of FO B cells triggered by LPS/TLR4. Our study reveals unexpected opposite roles for TLR4 and TLR9 in the control of plasma cell differentiation program and disagrees with previous conclusions obtained in high-density cultures conditions on the generation of plasmocytes by TRL9 signaling. The potential implications of these findings on the role of TLR9 in controlling self-tolerance, clonal sizes and regulation of humoral responses are discussed.

Analysis of air temperature changes on blood pressure and heart rate and performance of undergraduate students.

BACKGROUND: The increase in air temperature has been associated with human deaths, some of which are related to cardiovascular dysfunctions, and with the reduction of physical and cognitive performance in humans. OBJECTIVE: To analyze the relationship between blood pressure (BP) and heart rate (HR) and the cognitive performance of students who were submitted to temperature changes in classrooms. METHODS: The university students answered a survey that was adapted from the Battery of Reasoning Tests over 3 consecutive days at different air temperatures while their thermal state and HR were measured. During those 3 days, BP and HR were evaluated before and after the cognitive test. RESULTS: The average and final HR increased at high temperatures; the tests execution time was reduced at high temperatures; and the cognitive tests was related to Mean BP at the beginning of the test, the maximum HR during the test and the air temperature. CONCLUSIONS: The cognitive performance of undergraduate students in the field of engineering and technology will increase while performing activities in a learning environment with an air temperature of approximately 23.3°C (according to their thermal perception), if students have an initial MBP of 93.33 mmHg and a 60 bpm HRmax.

On flavourful Easter eggs for New Physics hunger and lepton flavour universality violation.

Within the standard approach of effective field theory of weak interactions for Δ B = 1 transitions, we look for possibly unexpected subtle New Physics effects, here dubbed "flavourful Easter eggs". We perform a Bayesian global fit using the publicly available HEPfit package, taking into account state-of-the-art experimental information concerning these processes, including the suggestive measurements from LHCb of R K and R K ∗ , the latter available only very recently. We parametrise New Physics contributions to b → s transitions in terms of shifts of Wilson coefficients of the electromagnetic dipole and semileptonic operators, assuming CP-conserving effects, but allowing in general for violation of lepton flavour universality. We show how optimistic/conservative hadronic estimates can impact quantitatively the size of New Physics extracted from the fit. With a conservative approach to hadronic uncertainties we find nonzero New Physics contributions to Wilson coefficients at the level of ∼ 3 σ , depending on the model chosen. Furthermore, given the interplay between hadronic contributions and New Physics effects in the leptonic vector current, a scenario with nonstandard leptonic axial currents is comparable to the more widely advocated one with New Physics in the leptonic vector current.

Quantitative trait locus analysis of parasite density reveals that HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia.

BACKGROUND: Haemoglobin S (HbS) is the gene known to confer the strongest advantage against malaria morbidity and mortality. Multiple HbS effects have been described resulting in protection against parasitaemia and reduction of severe malaria risk. This study aimed to explore HbS protection against severe malaria and Plasmodium falciparum parasitaemia in Angolan children exhibiting different severe malaria syndromes. METHODS: A case-control study was designed with 430 malaria cases (n = 288 severe malaria and n = 142 uncomplicated malaria) and 319 uninfected controls, attending a central paediatric hospital in Luanda. Severe malaria syndromes were cerebral malaria (n = 130), severe malaria anaemia (n = 30) and hyperparasitaemia (n = 128). Quantitative trait locus analysis was carried out to study HbS association to parasite densities. RESULTS: Previously reported HbS protection against severe malaria was confirmed in case-control analysis (P = 2 × 10(-13)) and corroborated by transmission disequilibrium test (P = 4 × 10(-3)). High parasite density protection conferred by HbS was detectable within severe malaria patients (P = 0.04). Stratifying severe malaria patients according parasite densities, it was found that HbS was highly associated to hyperparasitaemia protection (P = 1.9 × 10(-9)) but did not protect non-hyperparasitaemic children against severe malaria complications, namely cerebral malaria and severe malaria anaemia. Many studies have shown that HbS protects from severe malaria and controls parasite densities but the analysis further suggests that HbS protection against severe malaria syndromes was at a large extent correlated with control of parasitaemia levels. CONCLUSIONS: This study supports the hypothesis that HbS confers resistance to hyperparasitaemia in patients exhibiting severe malaria syndromes and highlights that parasitaemia should be taken into account when evaluating HbS protection in severe malaria.

Outcomes of endoscopic management of primary and refractory postcholecystectomy biliary leaks in a multicentre review of 178 patients.

BACKGROUND: Biliary leaks have been treated with endoscopic management using different techniques with conflicting results. Furthermore the appropriate rescue therapy for refractory leaks has not been established. We evaluated the clinical effectiveness of initial endotherapy for postcholecystectomy biliary leaks using an homogenous approach (sphincterotomy + placement of a 10-French plastic stent) in a large series of patients as well as the optimal and efficacy of rescue endotherapy for refractory biliary leaks. METHODS: This was a multicenter, retrospective study of 178 patients who underwent endoscopic management of postcholecystectomy biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore (10-French) plastic stent. Data were collected to analyze the clinical outcomes and technical success, efficacy of the rescue endotherapy and the need for surgery, adverse events and prognostic factors for clinical success of endotherapy. RESULTS: Following endotherapy, closure of the leak was accomplished in 162/178 patients (91.0%). The multivariate logistic model showed that the type of leak, namely a high-grade biliary leak, was the only independent prognostic factor associated with treatment failure (OR = 26.78; 95% CI = 6.59-108.83; P < 0.01). The remaining 16 patients were treated with multiple plastic stents (MPSs) with a success rate of 62.5% (10 patients). The use of fewer than 3 plastic stents (P = 0.023) and a high-grade biliary leak (P = 0.034) were shown to be significant predictors of treatment failure with MPSs in refractory bile leaks. The 6 patients in whom the placement of MPSs failed were retreated with a fully cover self-expandable metallic stent (FCSEMS), resulting in closure of the leak in all cases. CONCLUSIONS: Endotherapy of biliary leaks with a combination of biliary sphincterotomy and the placement of a large-bore plastic stent is associated with a high rate of success (90%). However in our series there were several failures using MPSs as a strategy for rescue endotherapy suggesting that refractory biliary leaks should be treated with FCSEMS especially in patients with high-grade leaks.

Early-onset autoimmune disease as a manifestation of primary immunodeficiency.

Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-α pathway (in Aicardi-Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID.

A non-randomized study in consecutive patients with postcholecystectomy refractory biliary leaks who were managed endoscopically with the use of multiple plastic stents or fully covered self-expandable metal stents (with videos).

BACKGROUND: Endoscopic management of postcholecystectomy biliary leaks is widely accepted as the treatment of choice. However, refractory biliary leaks after a combination of biliary sphincterotomy and the placement of a large-bore (10F) plastic stent can occur, and the optimal rescue endotherapy for this situation is unclear. OBJECTIVE: To compare the clinical effectiveness of the use of a fully covered self-expandable metal stent (FCSEMS) with the placement of multiple plastic stents (MPS) for the treatment of postcholecystectomy refractory biliary leaks. DESIGN: Prospective study. SETTING: Two tertiary-care referral academic centers and one general district hospital. PATIENTS: Forty consecutive patients with refractory biliary leaks who underwent endoscopic management. INTERVENTIONS: Temporary placement of MPS (n = 20) or FCSEMSs (n = 20). MAIN OUTCOME MEASUREMENTS: Clinical outcomes of endotherapy as well as the technical success, adverse events, need for reinterventions, and prognostic factors for clinical success. RESULTS: Endotherapy was possible in all patients. After endotherapy, closure of the leak was accomplished in 13 patients (65%) who received MPS and in 20 patients (100%) who received FCSEMSs (P = .004). The Kaplan-Meier (log-rank) leak-free survival analysis showed a statistically significant difference between the 2 patient populations (χ(2) [1] = 8.30; P < .01) in favor of the FCSEMS group. Use of <3 plastic stents (P = .024), a plastic stent diameter <20F (P = .006), and a high-grade biliary leak (P = .015) were shown to be significant predictors of treatment failure with MPS. The 7 patients in whom placement of MPS failed were retreated with FCSEMSs, resulting in closure of the leaks in all cases. LIMITATIONS: Non-randomized design. CONCLUSION: In our series, the results of the temporary placement of FCSEMSs for postcholecystectomy refractory biliary leaks were superior to those from the use of MPS. A randomized study is needed to confirm our results before further recommendations.

Fetal-onset IPEX: report of two families and review of literature.

Early-life autoimmunity is an IPEX characteristic, however intrauterine forms had not yet been described. Here, two unrelated families with clear evidence of fetal-onset IPEX are reported. One had 5 miscarriages of males in two generations, and a newborn presenting type-1 diabetes mellitus immediately after birth, diarrhea, thrombocytopenia, eczematous dermatitis, eosinophilia, high IgE levels and autoantibodies to pancreatic islet antigens at 4-days-old. Maternal serology was negative. He presented a FOXP3 mutation, c.1189C>T, p.Arg397Trp, previously described only in another family with IPEX at birth. The second family had several miscarriages of males in three consecutive generations and a novel FOXP3 c.319_320delTC mutation was observed in two miscarried monochorionic twin male fetuses. These twins died at 21weeks of gestation due to hydrops, and CD3+ infiltrating lymphocytes were found in their pancreas. We demonstrate that: i) IPEX may develop in fetal life; and ii) c.1189C>T and c.319_320delTC mutations are associated with early-onset phenotype.

Endoscopic bilio-duodenal bypass: outcomes of primary and revision efficacy of combined metallic stents in malignant duodenal and biliary obstructions.

BACKGROUND: Self-expandable metal stents (SEMSs) can be used for palliation of combined malignant biliary and duodenal obstructions. However, the results of the concomitant stent placement for the duration of the patients' lives, as well as the need for and efficacy of endoscopic revision, are unclear. AIM: This study evaluated the clinical effectiveness of SEMS placement for combined biliary and duodenal obstructions throughout the patients' lives and the need for endoscopic revision. METHODS: This study is a retrospective multicenter study of 50 consecutive patients who underwent simultaneous or sequential SEMS placement for malignant biliary and duodenal obstructions. The data were collected to analyze the sustained relief of obstructive symptoms until the patients' death and the efficacy of endoscopic revision, as well as stent patency, adverse events, survival and prognostic factors for stent patency. RESULTS: Technical and immediate clinical success was achieved in all of the patients. Duodenal stricture occurred before the papilla in 35 patients (70 %), involved the papilla in 11 patients (22 %) and was observed distal to the papilla in four patients (8 %). Initial biliary stenting was performed endoscopically in 42 patients (84 %) and percutaneously in eight patients. After combined stenting, 30 patients (60 %) required no additional intervention until the time of their death. The remaining 20 patients were successfully treated using endoscopic stent reinsertion: nine patients needed biliary revision, three patients needed duodenal restenting and eight patients needed both biliary and duodenal reinsertion. The median duodenal stent patency and median biliary stent patency were 34 and 27 weeks, respectively. The median survival after combined stent placement was 18 weeks. A Cox multivariate analysis showed that duodenal stent obstruction after combined stenting was a risk factor for biliary stent obstruction (hazard ratio 6.85; 95 % confidence interval 1.43-198.98; P = 0.025). CONCLUSIONS: Endoscopic bilio-duodenal bypass is clinically effective, and the majority of the patients need no additional intervention until their death. Endoscopic revision is feasible and has a high success rate.

NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.

Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.

Predictive value of cholangioscopy after endoscopic management of early postcholecystectomy bile duct strictures with an increasing number of plastic stents: a prospective study (with videos).

BACKGROUND: Endotherapy of postcholecystectomy bile duct stricture (PCBS) has been established as an alternative treatment to surgery. Several studies have reported conflicting results regarding the predictors of success or failure of endotherapy. OBJECTIVE: To evaluate the different cholangioscopic appearances of PCBS after endotherapy with an increasing number of plastic stents and the predictive values of these appearances for the outcome. DESIGN: Prospective study with a long-term follow-up. SETTING: Two academic tertiary referral centers. PATIENTS: Twenty consecutive patients with major bile duct injury, with a bile leak, and a PCBS who underwent therapeutic ERCP. INTERVENTIONS: Closure of the leak followed by temporary placement of multiple plastic stents for the treatment of PCBS, followed by cholangioscopy at the end of endotherapy. MAIN OUTCOME MEASUREMENTS: To analyze the predictive value of cholangioscopy, other predictors of stricture recurrence after endotherapy, and long-term clinical success. RESULTS: Closure of the leak was achieved in all patients. The median duration of endotherapy was 12 months (range 7-18 months). After endoscopic stenting, the PCBS was considered to be appropriately dilated in all patients. After endotherapy, 3 different findings were noted on cholangioscopy: (1) no lesion or minor defect (n = 10), (2) minor stricture with a fibrous ring (n = 6), and (3) presence of tissue hyperplasia (n = 4). During follow-up, stricture recurrence developed in 4 of 20 patients. All 4 patients were successfully retreated by an additional period of stenting and remained free of cholestasis after a median follow-up period of 44 months. By Kaplan-Meier (log-rank) and univariate analyses, the cholangioscopic pattern of tissue hyperplasia was significantly associated with stricture recurrence (P < .01). LIMITATIONS: Small sample size. CONCLUSIONS: Endoscopic stenting should be regarded as the primary treatment of choice because of the successful long-term outcome after 1 or more additional periods of treatment. However, the cholangioscopic pattern of tissue hyperplasia at the time of stent removal is a strong predictor of stricture recurrence, and this observation may lead to an additional period of endotherapy or other treatment modalities.

Old dogs and new tricks: defective peripheral regulatory T cell generation in aged mice.

Tolerance is a developmentally acquired property of the vertebrate immune system, in part ensured by regulatory CD4⁺ lymphocytes (Treg cells) expressing the Foxp3 transcription factor. Recent work has shown that thymic emigrants are the preferential source of peripherally generated Treg cells. A new report in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 2598-2604] describes a cell autonomous defect in Foxp3 induction in aged CD4⁺ cells in mice. Immune homeostasis becomes progressively less robust as ontogeny gives way to aging, and a key feature of senescence is thymic involution and the impaired T-cell turnover that follows. In this Commentary, we discuss the implications of these recent findings for our understanding of the induction of tolerance to peripheral antigens in aging.

IFNAR1 controls progression to cerebral malaria in children and CD8+ T cell brain pathology in Plasmodium berghei-infected mice.

Development of cerebral malaria (CM), a severe and fatal form of clinical Plasmodium falciparum infection, results from a damaging cascade of vascular, inflammatory, and immunological host responses that leads to brain injury. Progression to CM can be modified by host genetic factors. Our case-control study in Angolan children aimed at highlighting the role of IFN (α, ß) receptor 1 (IFNAR1) in progression to CM. We report a robust association between IFNAR1 and CM protection, as well as detailed studies showing analogous protection from experimental CM in Ifnar1(-/-) mice infected with P. berghei ANKA. We developed a novel cell-transfer protocol that enables spleen cell priming in the absence of disease. This led to the discovery that IFNAR1 expression in CD8(+) T cells is crucial and can abrogate resistance to experimental CM in Ifnar1(-/-) mice. Splenic CD8(+) T cells from Ifnar1(-/-) mice are functionally activated upon infection, yet are unable to mediate experimental CM development within the brain tissue. Our findings prove that IFNAR1 signaling unleashes CD8(+) T cell effector capacity, which is vital for CM, and raises the hypothesis that the cohesive role of IFNAR1 in both human and mouse CM operates through CD8(+) T cell triggering.