Either a CD4+or CD8+T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice

Ghiasi, Homayon; Perng, Guey Chuen; Nesburn, Anthony B.; Wechsler, Steven L.

doi:10.1006/mpat.1999.0314

Cited by 26 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). Our data align with one study of ocular HSV-1 infection, in which clearance of infectious HSV-1 from the trigeminal ganglia was apparently achieved by either the CD4 ϩ or the CD8 ϩ T-cell population (16). Although either subset appears sufficient for clearance of infectious HSV, it is important to emphasize that both the CD4 ϩ and the CD8 ϩ T-cell populations are likely to function in clearance in an intact animal.…”

Section: Discussionsupporting

confidence: 86%

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Johnson¹,

Chu²,

Milligan

2008

J Virol

View full text Add to dashboard Cite

In primary infection, CD8؉ T cells are important for clearance of infectious herpes simplex virus (HSV) from sensory ganglia. In this study, evidence of CD4 ؉ T-cell-mediated clearance of infectious HSV type 1 (HSV-1) from neural tissues was also detected. In immunocompetent mice, HSV-specific CD4 ؉ T cells were present in sensory ganglia and spinal cords coincident with HSV-1 clearance from these sites and remained detectable at least 8 months postinfection. Neural CD4 ؉ T cells isolated at the peak of neural infection secreted gamma interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), or IL-4 after stimulation with HSV antigen. HSV-1 titers in neural tissues were greatly reduced over time in CD8؉ T-cell-deficient and CD8

show abstract

Section: Discussionsupporting

confidence: 86%

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Johnson¹,

Chu²,

Milligan

2008

J Virol

View full text Add to dashboard Cite

show abstract

“…ϩ T cells within draining lymph nodes followed by their migration to sites of infection, including the sensory ganglia, where they act to clear infectious virus (8,13,20,33,41,49,58). Here we show that these infiltrating T cells persist beyond the cessation of lytic infection, well into latency, consistent with other studies (29,54).…”

Section: Skin Infection With Herpes Simplex Virus Involves the Activasupporting

confidence: 88%

“…Regardless of whether the persisting T cells limit reactivation as suggested by Khanna and colleagues (29,34), they are unlikely to remain inert during this process since they are capable of shutting down lytic replication within the ganglia (20,49,58). Therefore, in order to permit replication to occur, these cells must be overwhelmed in some fashion by the reemerging virus.…”

Section: Fig 6 In Vivo Activation Of Gbt-i Cd8mentioning

confidence: 99%

Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8⁺T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia

Lint

Kleinert

Clarke

et al. 2005

J Virol

View full text Add to dashboard Cite

CD8؉ T-cell persistence can be seen in ganglia harboring latent herpes simplex virus (HSV) infection. While there is some evidence that these cells suppress virus reactivation, this view remains controversial. Given that maintenance of latency by CD8 ؉ T cells would necessitate ongoing exposure to antigen within this site, we sought evidence for such chronic stimulation. Initial experiments showed infiltration by activated but not naïve CD8 ؉ T cells into ganglia harboring latent HSV infection. While such infiltration was independent of T-cell specificity, once recruited, only virus-specific T cells expressed high levels of preformed granzyme B, a marker of ongoing activation. Moreover, bone marrow replacement chimeras showed that these elevated granzyme levels were totally dependent on presentation by parenchymal cells within the ganglia. Overall, this study argues that activated CD8 ؉ T cells are nonspecifically recruited into latently infected ganglia, and in this site they are exposed to ongoing antigen stimulation, most likely by infected neuronal cells.

show abstract

“…In fact, after the initial viral replication and the outbreak of vesicular rash, it is the antiviral T cells that usually limit and control viral replication (6,(12)(13)(14)(15)(16). By contrast, in the absence of T cell immunity, uncontrolled viral replication typically leads to lethal encephalitis (13,15,17,18). Nevertheless, the exact role, basic biology, and mechanisms of antiviral action of various T cell subsets remain incompletely understood, including the kinetics of priming, kinetics and parameters of migration into infected organs, and interplay with the replicating virus.…”

Section: H Erpes Simplex Virus Type 1 Infection Of Scarified Murine Cmentioning

confidence: 99%

“…CD8 ϩ T cells were implicated as potential mediators of acute viral control in the nervous system and of neuropathogenesis (12,13,15,(17)(18)(19)(20)(21) and also as sentinels that potentially control viral reactivation from latency in the TG in situ (22)(23)(24)(25). Such evidence was obtained using infection of animals treated with depleting Abs (13,15,17) or studies in knockout mice lacking CD8␣ (26,27), IFN-␥ (26, 28 -30), or molecules that mediate cytotoxicity (27,(31)(32)(33)(34). Direct proof that the missing effector molecules act via CD8 T cells, however, was often not obtained in these studies, and the results of some studies questioned an obligatory role of CD8 ϩ T cells in fighting HSV (22,35).…”

Section: H Erpes Simplex Virus Type 1 Infection Of Scarified Murine Cmentioning

confidence: 99%

Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection

Lang

Nikolich‐Žugich

2005

The Journal of Immunology

View full text Add to dashboard Cite

After infection of epithelial surfaces, HSV-1 elicits a multifaceted antiviral response that controls the virus and limits it to latency in sensory ganglia. That response encompasses the CD8+ T cells, whose precise role(s) is still being defined; immune surveillance in the ganglia and control of viral spread to the brain were proposed as the key roles. We tracked the kinetics of the CD8+ T cell response across lymphoid and extralymphoid tissues after ocular infection. HSV-1-specific CD8+ T cells first appeared in the draining (submandibular) lymph node on day 5 and were detectable in both nondraining lymphoid and extralymphoid tissues starting on day 6. However, although lymphoid organs contained both resting (CD43lowCFSEhigh) and virus-specific cells at different stages of proliferation and activation, extralymphoid sites (eye, trigeminal ganglion, and brain) contained only activated cells that underwent more than eight proliferations (CD43highCFSEneg) and promptly secreted IFN-γ upon contact with viral Ags. Regardless of the state of activation, these cells appeared too late to prevent HSV-1 spread, which was seen in the eye (from day 1), trigeminal ganglia (from day 2), and brain (from day 3) well before the onset of a detectable CD8+ T cell response. However, CD8+ T cells were critical in reducing viral replication starting on day 6 and for its abrogation between days 8 and 10; CD8-deficient animals failed to control the virus, exhibited persisting high viral titers in the brain after day 6, and died of viral encephalitis between days 7 and 12. Thus, CD8+ T cells do not control HSV-1 spread from primary to tertiary tissues, but, rather, attack the virus in infected organs and control its replication in situ.

show abstract

Either a CD4+or CD8+T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice

Cited by 26 publications

References 35 publications

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8⁺T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia

Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection

Contact Info

Product

Resources

About

Either a CD4+or CD8+T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice

Cited by 26 publications

References 35 publications

Effector CD4+T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Effector CD4+T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8+T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia

Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection

Contact Info

Product

Resources

About

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Effector CD4⁺T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8⁺T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia