scholarly journals Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons.

1992 ◽  
Vol 175 (5) ◽  
pp. 1337-1344 ◽  
Author(s):  
A Simmons ◽  
D C Tscharke
Keyword(s):  
T Cells ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd8 T Cells ◽  
Genetic Determinants ◽  
Histocompatibility Complex ◽  
Sensory Nervous System ◽  
Simplex Virus

The role of CD8+ T cells in resistance to herpes simplex virus (HSV) was examined. After cutaneous inoculation, HSV spreads to the peripheral nervous system (PNS) where it replicates in ganglionic neurons. In normal mice, replication of virus in the PNS was rapidly terminated and evidence of neuronal destruction, assessed by a quantitative histological assay, was sparse. Clearance of infectious virus was impaired, and a strikingly high proportion of ganglionic neurons was killed, in mice treated with an antibody that depleted them of CD8+ T cells. These results suggest that CD8+ T cells play an important role in maintaining the integrity of the sensory nervous system during primary infection with HSV. Therefore, viral epitopes recognized by CD8+ T cells and restricting class I major histocompatibility complex genes are, in principle, implicated as interacting genetic determinants of neurovirulence.

scholarly journals Dysfunctional Senescent Herpes Simplex Virus Specific CD57+CD8+ T cells are Associated with Recurrent Symptomatic Herpes in Humans

2022 ◽  
Author(s):  
Lbachir BenMohamed ◽  
Arif A. Khan ◽  
Ruchi Srivastava ◽  
Hawa Vahed
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd8 T Cells ◽  
High Frequency ◽  
Recurrent Herpes ◽  
Natural Protection ◽  
Simplex Virus ◽  
And Function

Herpes simplex virus (HSV)-specific CD8+ T cells protect mice from herpes infection and disease. However, the phenotype and function of HSV-specific CD8+ T cells that play a key role in the "natural" protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. We previously reported that symptomatic (SYMP) patients (who have frequent bouts of recurrent herpes disease) had more less-differentiated and dysfunctional HSV-specific CD8+ T cells. In contrast, healthy ASYMP individuals maintained a significantly higher proportion of differentiated polyfunctional CD8+ T cells. Here we report that, HSV-specific CD8+ T cells from SYMP patients, but not from ASYMP individuals, have phenotypic and functional characteristics of cellular senescence, including: (i) high frequency of senescent (CD57+) and exhausted (PD-1+) CD8+ T cells; (ii) late terminally differentiated (KLRG1+), non-proliferating CD8+ T cells; (iii) HSV-specific CD8+ T cells were declined overtime and were not maintained homeostatistically (CD127+CD8+ T cells); (iv) loss of co-stimulatory molecule (CD28)on HSV-specific CD8+ T cells; (v) decreased production of effector molecules (granzyme B and perforin) by HSV-specific CD8+ T cells. Our findings provide insights into the role of senescence in HSV-specific CD8+ T cells in susceptibility to recurrent herpes and have implications for T-cell-based immunotherapeutic strategies against recurrent herpes in humans.

scholarly journals CD8+ T Cells in the Central Nervous System of Mice With Herpes Simplex Infection are Highly Activated and Express High Levels of CCR5 and CXCR3

2020 ◽  
Author(s):  
Liza Lind ◽  
Alexandra Svensson ◽  
Karolina Thörn ◽  
Malgorzata Krzyzowska ◽  
Kristina Eriksson
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
The Central Nervous System ◽  
Simplex Virus

Abstract Background: Herpes simplex virus type 2 (HSV-2) is a neurotropic virus that can cause meningitis, an inflammation of the meninges in the central nervous system. T cells are key players in viral clearance, and these cells migrate from peripheral blood into the central nervous system upon infection. Several factors contribute to T cell migration, including the expression of chemokines in the inflamed tissue that attract T cells through their expression of chemokine receptors. Here we investigated CD8+ T cell profile in the spinal cord in a mouse model of herpes simplex virus type 2neuroinflammation. Method: Mice were infected with HSV-2, and sacrificed when showing signs of neuroinflammation. Cells and/or tissue from spinal cord, spleen and bloodwere analyzed for viability, expression of activation markers, chemokinereceptors and chemokines. Statistics were calculated using students T test and one-way ANOVA.Results:High numbers of CD8+ T cellswere present in thespinal cord following genital HSV-2-infection.CD8+T cells were highly activated and HSV-2 glycoprotein B -specific effector cells, some of which showed signs of recent degranulation. They also expressed high levels of many chemokine receptors, in particular CCR2, CCR4, CCR5 and CXCR3. Investigating corresponding receptor ligands in spinal cord tissue revealed markedly increased expression of the cognate ligands CCL2, CCL5, CCL8,CCL12 and CXCL10. Conclusion: This study shows thatduring herpesvirus neuroinflammation anti-viralCD8+T cells accumulatein the CNS. CD8+ T cells in the CNS also express chemotactic receptors cognate to the chemotactic gradients in the spinal cord. This indicates that anti-viral CD8+ T cells may migrate to infected areas in the spinal cord during herpesvirus neuroinflammation in response to chemotactic gradients.

scholarly journals Role of Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein K (gK) Pathogenic CD8+ T Cells in Exacerbation of Eye Disease

2018 ◽  
Vol 9 ◽  
Author(s):  
Ujjaldeep Jaggi ◽  
Shaohui Wang ◽  
Kati Tormanen ◽  
Harry Matundan ◽  
Alexander V. Ljubimov ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cd8 T Cells ◽  
Herpes Simplex Virus Type ◽  
Eye Disease ◽  
Glycoprotein K ◽  
Simplex Virus

scholarly journals Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons

2000 ◽  
Vol 191 (9) ◽  
pp. 1459-1466 ◽  
Author(s):  
Ting Liu ◽  
Kamal M. Khanna ◽  
XiaoPing Chen ◽  
David J. Fink ◽  
Robert L. Hendricks
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Cd8 T Cells ◽  
Early Proteins ◽  
Latently Infected ◽  
Simplex Virus ◽  
Hsv 1

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8+ T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8+ T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8α monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8+ T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8+ T cells aborting virion production.

scholarly journals Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Yike Jiang ◽  
Chaya D. Patel ◽  
Richard Manivanh ◽  
Brian North ◽  
Iara M. Backes ◽  
...  
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Neural Tissue ◽  
Maternal Antibodies ◽  
Herpes Simplex Virus 1 ◽  
Maternal Immunization ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.

scholarly journals Selective Expression of CCR10 and CXCR3 by Circulating Human Herpes Simplex Virus-Specific CD8 T Cells

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Michael T. Hensel ◽  
Tao Peng ◽  
Anqi Cheng ◽  
Stephen C. De Rosa ◽  
Anna Wald ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
Mrna Levels ◽  
Skin Homing ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T cells. CLA/ESL mediates adhesion of T cells to inflamed vascular endothelium. Later stages in T-cell homing involve chemokines (Ch) and lymphocyte chemokine receptors (ChR) for vascular wall arrest and diapedesis. Several candidate ChR have been implicated in skin homing. We measured cell surface ChR on HSV-specific human peripheral blood CD8 T cells and extended our studies to HSV-1. We observed preferential cell surface expression of CCR10 and CXCR3 by HSV-specific CD8 T cells compared to CD8 T cells specific for control viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), and compared to bulk memory CD8 T cells. CXCR3 ligand mRNA levels were selectively increased in skin biopsy specimens from persons with recurrent HSV-2, while the mRNA levels of the CCR10 ligand CCL27 were equivalent in lesion and control skin. Our data are consistent with a model in which CCL27 drives baseline recruitment of HSV-specific CD8 T cells expressing CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in response to virus-driven inflammation. IMPORTANCE HSV-2 causes very localized recurrent infections in the skin and genital mucosa. Virus-specific CD8 T cells home to the site of recurrent infection and participate in viral clearance. The exit of T cells from the blood involves the use of chemokine receptors on the T-cell surface and chemokines that are present in infected tissue. In this study, circulating HSV-2-specific CD8 T cells were identified using specific fluorescent tetramer reagents, and their expression of several candidate skin-homing-associated chemokine receptors was measured using flow cytometry. We found that two chemokine receptors, CXCR3 and CCR10, are upregulated on HSV-specific CD8 T cells in blood. The chemokines corresponding to these receptors are also expressed in infected tissues. Vaccine strategies to prime CD8 T cells to home to HSV lesions should elicit these chemokine receptors if possible to increase the homing of vaccine-primed cells to sites of infection.

Role of Lyt-1 Positive Immune T Cells in Recovery from Herpes Simplex Virus Infection in Mice

1982 ◽  
Vol 26 (4) ◽  
pp. 359-362 ◽  
Author(s):  
Seiho Nagafuchi ◽  
Isao Hayashida ◽  
Kazuo Higa ◽  
Toshio Wada ◽  
Ryoichi Mori
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Infection ◽  
Herpes Simplex Virus Infection ◽  
Simplex Virus

scholarly journals Latency of herpes simplex virus type-1 in human geniculate and vestibular ganglia is associated with infiltration of CD8+ T cells

2010 ◽  
Vol 82 (11) ◽  
pp. 1917-1920 ◽  
Author(s):  
Viktor Arbusow ◽  
Tobias Derfuss ◽  
Kathrin Held ◽  
Susanne Himmelein ◽  
Michael Strupp ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Cd8 T Cells ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus
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