scholarly journals An immunotherapy effect analysis in Rasmussen encephalitis

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zuzana Liba ◽  
Martina Vaskova ◽  
Josef Zamecnik ◽  
Jana Kayserova ◽  
Hana Nohejlova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Laboratory Data ◽  
Intractable Epilepsy ◽  
Lymphocyte Subpopulations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rasmussen Encephalitis ◽  
Multiple Samples ◽  
The Brain ◽  
Brain Tissues

Abstract Background Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy. Methods Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected. Results Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients’ CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF. Conclusions We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.

scholarly journals Phenotypic and functional complexity of brain-infiltrating T cells in Rasmussen encephalitis

2017 ◽  
Vol 5 (1) ◽  
pp. e419 ◽  
Author(s):  
Faiez Al Nimer ◽  
Ivan Jelcic ◽  
Christian Kempf ◽  
Tom Pieper ◽  
Herbert Budka ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Brain Tissue ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Special Focus ◽  
Rasmussen Encephalitis ◽  
Ifn Γ ◽  
The Brain

Objective:To characterize the brain-infiltrating immune cell repertoire in Rasmussen encephalitis (RE) with special focus on the subsets, clonality, and their cytokine profile.Methods:The immune cell infiltrate of freshly isolated brain tissue from RE was phenotypically and functionally characterized using immunohistology, flow cytometry, and T-cell receptor (TCR) deep sequencing. Identification of clonally expanded T-cell clones (TCCs) was achieved by combining flow cytometry sorting of CD4+ and CD8+ T cells and high-throughput TCR Vβ-chain sequencing. The most abundant brain-infiltrating TCCs were isolated and functionally characterized.Results:We found that CD4+, CD8+, and also γδ T cells infiltrate the brain tissue in RE. Further analysis surprisingly revealed that not only brain-infiltrating CD8+ but also CD4+ T cells are clonally expanded in RE. All 3 subsets exhibited a Tc1/Th1 phenotype characterized by the production of interferon (IFN)-γ and TNF. Broad cytokine profiling at the clonal level showed strong production of IFN-γ and TNF and also secretion of interleukin (IL)-5, IL-13, and granzyme B, both in CD4+ and CD8+ T cells.Conclusions:CD8+ T cells were until now considered the central players in the immunopathogenesis of RE. Our study adds to previous findings and highlights that CD4+ TCCs and γδ T cells that secrete IFN-γ and TNF are also involved. These findings underline the complexity of T-cell immunity in RE and suggest a specific role for CD4+ T cells in orchestrating the CD8+ T-cell effector immune response.

scholarly journals Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Margherita Amadi ◽  
Silvia Visentin ◽  
Francesca Tosato ◽  
Paola Fogar ◽  
Giulia Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Helper Cells ◽  
Lymphocyte Subpopulations ◽  
T Helper ◽  
Premature Rupture Of Membranes ◽  
Premature Rupture ◽  
Preterm Premature Rupture ◽  
Helper Cells

Abstract Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were to examine the effects of pPROM (Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin N Am 2005;32:411) on the newborn’s and mother’s immune system and (Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A, et al. Factors affecting the latency period in patients with preterm premature rupture of membranes (pPROM). Arch Gynecol Obstet 2011;283:707–10) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

Both CD4+ and CD8+ T-cell clones infiltrate the brain in a case of bilateral Rasmussen encephalitis

2014 ◽  
Vol 275 (1-2) ◽  
pp. 133-134
Author(s):  
Faiez Al Nimer ◽  
Ivan Jelcic ◽  
Christian Kempf ◽  
Tom Pieper ◽  
Mireia Sospedra ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Rasmussen Encephalitis ◽  
T Cell Clones ◽  
Cell Clones ◽  
The Brain

scholarly journals IMMU-28. INDUCTION OF TERTIARY LYMPHOID STRUCTURE-LIKE T-CELL CLUSTERS BY DELIVERY OF A NOVEL GENE COMBINATION INTO AN IMMUNOCOMPETENT MOUSE MODEL OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii110-ii111
Author(s):  
Kira Downey ◽  
Bindu Hegde ◽  
Zinal Chheda ◽  
Jason Zhang ◽  
Hideho Okada
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphatic Drainage ◽  
Lymphoid Follicle ◽  
Brain Parenchyma ◽  
Cell Therapies ◽  
Gene Combination ◽  
Cell Clustering ◽  
The Brain

Abstract The lack of conventional lymphatic drainage to and from the brain parenchyma restricts the capacity of the peripheral immune system to recognize and respond to glioma antigens. In some peripheral solid tumor types and central nervous system autoimmunity, the spontaneous development of tertiary lymphoid structures (TLS) with varying degrees of organization have been observed in human patients and mice following chronic inflammation. In the cancer setting, presence of TLS are generally associated with improved prognosis, especially when they are characterized by intratumoral infiltration of CD8+ T-cells. We aimed to induce the development of TLS in vivo, utilizing our SB28 glioblastoma model which is sparsely infiltrated by lymphocytes. As a proof-of-concept study, we stably transduced SB28 with a combination of several TLS-stimulating factors that we’ve identified and injected these cells into the brain parenchyma of syngeneic C57BL/6J mice. A combination of the chemoattractant and lymphoid follicle-stimulating cytokines LIGHT, CCL21, IL-7, and IL-17 produced substantial infiltration of CD8+CD3+ T-cells into the tumor and nearby parenchyma. However, this combination was also associated with accelerated tumor growth. A modified gene combination including LIGHT, CCL21, and IL-7 promoted CD8+CD3+ T-cell infiltration by flow cytometry, T-cell clustering by immunofluorescence analysis, and inhibited tumor burden compared with the control as measured by bioluminescent imaging. There was also evidence of increased lymphatic vasculature around the margins of T-cell clustering as demonstrated by LYVE-1 staining. Together, these analyses highlight a role for these factors in stimulating the recruitment and clustering of T-cell to the glioblastoma microenvironment in a TLS-like phenomenon. Future studies will evaluate whether the recruitment of other lymphocytes and stromal cells to these TLS-like clusters can promote T-cell memory and persistence. Ultimately, we aim to provide these factors utilizing a gene delivery method that will prove translatable to the clinic and complementary to existing T-cell therapies.

EXTH-82. T CELL HITCHHIKING AS A MECHANISM OF DRUG DELIVERY TO THE BRAIN

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi182-vi182
Author(s):  
Kirit Singh ◽  
Patrick Gedeon ◽  
Teilo Schaller ◽  
David Snyder ◽  
Mustafa Khasraw ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Median Survival ◽  
Mass Spectroscopy ◽  
Ct Imaging ◽  
Spectroscopy Analysis ◽  
Activated T Cells ◽  
Pet Ct ◽  
The Brain ◽  
Mass Spectroscopy Analysis

Abstract INTRODUCTION The blood-brain barrier (BBB) restricts access to the central nervous system (CNS). Our brain bispecific T cell engager (hEGFRvIII:CD3 BRiTE) treats subcutaneous syngeneic tumor (CT2AvIII) but not intracranial CT2AvIII. CD3 engaging molecules such as nanoparticles can be carried into the brain by binding to activated T cells. We therefore sought to determine if co-administration of larger molecules (BRiTE, approx. 55kDa) with activated T cells could cross the BBB, enhancing survival. METHODS We implanted 8–10-week-old transgenic hCD3 mice (n=7-8 per group) with 30,000 CT2AvIII cells. Tumors were established for 6 days. Mice were administered either (1) autologous lymphocyte transfer (ALT) alone (single intravenous (IV) injection, 1 x 107 activated T cells), (2) serial IV BRiTE doses (50ug, 10 days) (3) BRiTE and ALT or (4) no treatment. Mice were followed for survival using Kaplan-Meier curves and compared via log rank test. Targeted mass spectroscopy analysis as well as PET/CT imaging of mice administered Iodine-124 radiolabelled BRiTE was performed to assess for intracranial accumulation. RESULTS Mice who received BRiTE and ALT demonstrated significantly enhanced survival compared to controls (median survival 29 vs 21 days, p=0.0135). Mice who received only BRiTE or ALT exhibited median survival comparable to controls (p=0.192, p=0.944 respectively). Mass spectroscopy analysis revealed that mice had a 7-fold increased peak area ratio of BRiTE in the CNS when co-treated with activated T cells compared to BRiTE alone (0.14, 0.02 respectively) while PET/CT imaging demonstrated increased radioactive signal over background localized to coordinates within the brain where tumors were injected. CONCLUSIONS Giving activated T cells alongside BRiTE allows better access to the intracranial compartment and is required to achieve efficacy in mice with syngeneic orthotopic glioma. Future work will determine the optimal dose and schedule for this approach, as well as defining the precise mechanism by which this occurs.

scholarly journals Bispecific T-Cell Engager -Armored Chimeric Antigen Receptor T Cells Overcome Antigen Escape From EGFRvIII-Targeted Therapy For Glioblastoma

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Bryan D Choi ◽  
Xiaoling Yu ◽  
Ana P Castano ◽  
Amanda A Bouffard ◽  
Andrea Schmidts ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Skin ◽  
Immune Therapy ◽  
Biologically Active ◽  
Target Antigen ◽  
Wild Type ◽  
Car T Cells ◽  
Car T ◽  
The Brain

Abstract INTRODUCTION Immune therapy with T cells engineered to express chimeric antigen receptors (CARs) represents a promising therapy for patients with glioblastoma (GBM). However, clinical responses have been limited due to heterogeneous target antigen expression and outgrowth of tumors lacking the antigen targeted by CAR T cells directed against a single target. In clinical studies with CART-EGFRvIII, EGFRvIII-targeted T cells successfully localized to the brain tumor microenvironment, but ultimately failed to prevent disease progression with post-treatment specimens demonstrating high levels of wild-type EGFR despite reduced expression of EGFRvIII. METHODS We developed a novel bicistronic CAR construct engineered for local delivery of bispecific T-cell engagers (BiTEs) that target residual tumor. Specifically, EGFRvIII-targeted CAR T cells were engineered to secrete BiTEs against wild-type EGFR, which is frequently amplified and overexpressed in GBM. RESULTS Human T cells were efficiently transduced with the dual CART.BiTE transgene. These modified cells secreted biologically active EGFR-specific BiTEs that not only redirected CAR T cells but also recruited and activated untransduced bystander T cells against wild-type EGFR. Recapitulating clinical data, EGFRvIII CAR T cells were unable to completely treat tumors with heterogenous EGFRvIII expression, leading to outgrowth of EGFRvIII-negative, EGFR-positive GBM. Conversely, CART.BiTE cells cured mice even in the setting of antigen-loss, against heterogeneous and well-established intracerebral tumors in mice. Unlike CAR T cells directly targeting EGFR, which caused toxicity in human skin grafts in vivo, secreted BiTE-EGFR was both locally effective and did not result in toxicity against grafted human skin. CONCLUSION This is the first instance in which CARs and BiTEs have been combined into a single platform of immune therapy. Our results demonstrate that CARs and BiTEs can be combined strategically to mitigate antigen heterogeneity in GBM and also provide a unique T-cell-based delivery method for BiTEs to tumors in the brain.

scholarly journals Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on T Cell Differentiation in Primary Biliary Cholangitis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chunhui She ◽  
Jing Wang ◽  
Ning Tang ◽  
Zhaoyang Liu ◽  
Lishan Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Autoimmune Disease ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
T Cell Differentiation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Biliary Cholangitis ◽  
Tetrachlorodibenzo P Dioxin

Exposure to dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is reported to affect the autoimmune system and increase the risk of autoimmune disease. Generally, dioxin exerts its toxicity via aryl hydrocarbon receptor (AhR). Primary biliary cholangitis (PBC) is a chronic autoimmune disease, and its pathogenesis involves the interplay between immune and environmental factors. This study showed the effect of dendritic cells (DCs) activated by TCDD on naïve CD4+ T cell differentiation in patients with PBC. CD14+ mononuclear cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with PBC and healthy people by magnetic cell separation and introduced into DCs. Two days after stimulation by TCDD, DCs were cocultured with naïve CD4+ T cells in a ratio of 1 : 2 for 3 days. Then, differentiation-related factors for naïve CD4+ T cells were detected by real-time fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry. The results showed that TCDD-activated DCs could promote Th1 and Th17 differentiation in patients with PBC. Therefore, this study demonstrated TCDD as an AhR agonist in regulating naïve CD4+ T cell differentiation in patients with PBC.

scholarly journals MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
E. Kip ◽  
J. Staal ◽  
L. Verstrepen ◽  
H. G. Tima ◽  
S. Terryn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Rabies Virus ◽  
T Cell Activation ◽  
Therapeutic Target ◽  
Cell Activation ◽  
Wild Type ◽  
The Impact ◽  
The Brain

ABSTRACTMALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1−/−mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1−/−mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1−/−mice at 10 dpi compared to MALT1+/+infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1+/+mice. Moreover, MALT1−/−mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain.IMPORTANCERabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protein involved in innate and adaptive immunity and is an interesting therapeutic target because MALT1-deregulated activity has been associated with autoimmunity and cancers. The role of MALT1 in viral infection is, however, largely unknown. Here, we study the impact of MALT1 on virus infection in the brain, using the attenuated ERA rabies virus in different models of MALT1-deficient mice. We reveal the importance of MALT1-mediated inflammation and T cell activation to control ERA virus, providing new insights in the biology of MALT1 and rabies virus infection.

scholarly journals CD8 T Cells and STAT1 Signaling Are Essential Codeterminants in Protection from Polyomavirus Encephalopathy

2020 ◽  
Vol 94 (8) ◽  
Author(s):  
Taryn E. Mockus ◽  
Colleen S. Netherby-Winslow ◽  
Hannah M. Atkins ◽  
Matthew D. Lauver ◽  
Ge Jin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Chemotherapeutic Agents ◽  
Immune Defense ◽  
Type I ◽  
Viral Control ◽  
Stat1 Signaling ◽  
The Brain

ABSTRACT JC polyomavirus (JCPyV), a human-specific virus, causes the aggressive brain-demyelinating disease progressive multifocal leukoencephalopathy (PML) in individuals with depressed immune status. The increasing incidence of PML in patients receiving immunotherapeutic and chemotherapeutic agents creates a pressing clinical need to define biomarkers to stratify PML risk and develop anti-JCPyV interventions. Mouse polyomavirus (MuPyV) CNS infection causes encephalopathology and may provide insight into JCPyV-PML pathogenesis. Type I, II, and III interferons (IFNs), which all signal via the STAT1 transcription factor, mediate innate and adaptive immune defense against a variety of viral infections. We previously reported that type I and II IFNs control MuPyV infection in non-central nervous system (CNS) organs, but their relative contributions to MuPyV control in the brain remain unknown. To this end, mice deficient in type I, II, or III IFN receptors or STAT1 were infected intracerebrally with MuPyV. We found that STAT1, but not type I, II, or III IFNs, mediated viral control during acute and persistent MuPyV encephalitis. Mice deficient in STAT1 also developed severe hydrocephalus, blood-brain barrier permeability, and increased brain infiltration by myeloid cells. CD8 T cell deficiency alone did not increase MuPyV infection and pathology in the brain. In the absence of STAT1 signaling, however, depletion of CD8 T cells resulted in lytic infection of the choroid plexus and ependymal lining, marked meningitis, and 100% mortality within 2 weeks postinfection. Collectively, these findings indicate that STAT1 signaling and CD8 T cells cocontribute to controlling MuPyV infection in the brain and CNS injury. IMPORTANCE A comprehensive understanding of JCPyV-induced PML pathogenesis is needed to define determinants that predispose patients to PML, a goal whose urgency is heightened by the lack of anti-JCPyV agents. A handicap to achieving this goal is the lack of a tractable animal model to study PML pathogenesis. Using intracerebral inoculation with MuPyV, we found that MuPyV encephalitis in wild-type mice causes an encephalopathy, which is markedly exacerbated in mice deficient in STAT1, a molecule involved in transducing signals from type I, II, and III IFN receptors. CD8 T cell deficiency compounded the severity of MuPyV neuropathology and resulted in dramatically elevated virus levels in the CNS. These findings demonstrate that STAT1 signaling and CD8 T cells concomitantly act to mitigate MuPyV-encephalopathy and control viral infection.

scholarly journals Glial Cell Expression of PD-L1

2019 ◽  
Vol 20 (7) ◽  
pp. 1677 ◽  
Author(s):  
Priyanka Chauhan ◽  
James Lokensgard
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Pathogen Detection ◽  
Therapeutic Potential ◽  
Immune Checkpoint Blockade ◽  
Programmed Death ◽  
Cell Expression ◽  
Inflammatory Milieu ◽  
The Brain

The programmed death (PD)-1/PD-L1 pathway is a well-recognized negative immune checkpoint that results in functional inhibition of T-cells. Microglia, the brain-resident immune cells are vital for pathogen detection and initiation of neuroimmune responses. Moreover, microglial cells and astrocytes govern the activity of brain-infiltrating antiviral T-cells through upregulation of PD-L1 expression. While T-cell suppressive responses within brain are undoubtedly beneficial to the host, preventing cytotoxic damage to this vital organ, establishment of a prolonged anti-inflammatory milieu may simultaneously lead to deficiencies in viral clearance. An immune checkpoint blockade targeting the PD-1: PD-L1 (B7-H1; CD274) axis has revolutionized contemporary treatment for a variety of cancers. However, the therapeutic potential of PD1: PD-L1 blockade therapies targeting viral brain reservoirs remains to be determined. For these reasons, it is key to understand both the detrimental and protective functions of this signaling pathway within the brain. This review highlights how glial cells use PD-L1 expression to modulate T-cell effector function and limit detrimental bystander damage, while still retaining an effective defense of the brain.

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