Persistence of a T Cell Infiltrate in Human Ganglia Years After Herpes Zoster and During Post-herpetic Neuralgia

Sutherland, Jeremy P; Steain, Megan; Buckland, Michael E.; Rodriguez, Michael; Cunningham, Anthony L.; Slobedman, Barry; Abendroth, Allison

doi:10.3389/fmicb.2019.02117

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…The pro-inflammatory effects of VZV-specific T cells may contribute to lesion and HZ pain, severity and duration. Human autopsy studies reveal the trigeminal ganglia, a site of VZV latency and reactivation, contains T cells abutting neurons after the resolution of HZ supporting a potential for local antigen-reactive T cells to contribute to PHN pathogenesis 42 . VZV-specific T cells persisting after HZ resolution may also aid host defense against future episodes of HZ in the same dermatome, as seen in murine studies with HSV, whereby local skin CD8 T RM provide anatomically restricted protection against reinfection 43 .…”

Section: Discussionmentioning

confidence: 99%

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

et al. 2022

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Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.

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Section: Discussionmentioning

confidence: 99%

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

et al. 2022

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“…Neuropathic pain represents a common clinical disease [21][22][23] . Peripheral nerve disorders can cause chronic pain, such as diabetes, uremia, neuralgia after herpes zoster, and ischemic neuropathy [38][39][40][41] . However, the pathogenesis, disease progression, and the effectiveness and appropriate duration of treatments remain unclear and difficult to assess 2,12,24,26,38 .…”

Section: Discussionmentioning

confidence: 99%

Long-term two-photon imaging of spinal cord in freely behaving mice

Jian

Han

et al. 2022

Preprint

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The spinal cord is critical to integrating peripheral information under sensory-guided motor behaviors in health and disease. However, the cellular activity underlie spinal cord function in freely behaving animals is not clear. Here, we developed a new method for imaging the spinal cord at cellular and subcellular resolution over weeks under naturalistic conditions. The method involves an improved surgery to reduce spinal movement, and the installation of a miniaturized two-photon microscope to obtain high-resolution imaging in moving mice. In vivo calcium imaging demonstrated that dorsal horn neurons show a sensorimotor program-dependent synchronization and heterogeneity under distinct cutaneous stimuli in behaving mice. The long-term imaging of sensory neurons revealed that in the spinal cord, healthy mice demonstrated stereotyped responses. However, in a neuropathic pain model, plasticity changes and neuronal sensitization were observed. We provide a practical method to study the function of spinal cord on sensory perception and disorders in freely behaving mice.

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“…Recent studies were able to identify CD8 1 cells as one of the major cell groups infiltrating ganglia after or during zoster infection. 18,41,42 Today, it is known that VZV antigens induce Tcell-mediated immune responses. 24,36 In a murine spinal model, Cao et al reported that T-lymphocyte-deficient mice presented a reduction in injury-induced hypersensitivity, suggesting T lymphocytes as an important factor for the maintenance of neuropathic pain.…”

Section: Cytotoxic T Cells and Sensitizationmentioning

confidence: 99%

Protective role of natural killer cells in neuropathic pain conditions

Lassen

Stürner

Gierthmühlen

et al. 2021

Pain

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During the past few years, the research of chronic neuropathic pain has focused on neuroinflammation within the central nervous system and its impact on pain chronicity. As part of the ERA-Net NEURON consortium, we aimed to identify immune cell patterns in the cerebrospinal fluid (CSF) of patients with herpes zoster neuralgia and patients with polyneuropathy (PNP), which may contribute to pain chronicity in these neuropathic pain conditions. Cerebrospinal fluid of 41 patients (10 herpes zoster and 31 PNP) was analyzed by flow cytometry identifying lymphocyte subsets: CD4+ (T-helper cells), CD8+ (cytotoxic T cells), CD19+ (B cells), and CD56+ (natural killer [NK]) cells. At baseline and at follow-up, the somatosensory phenotype was assessed with quantitative sensory testing. In addition, the patients answered epidemiological questionnaires and the PainDETECT questionnaire. Immune cell profiles and somatosensory profiles, as well as painDETECT questionnaire scores, were analyzed and correlated to determine specific immune cell patterns, which contribute to chronic pain. We found a negative correlation (P = 0.004, r = −0.596) between the frequency of NK cells and mechanical pain sensitivity (MPS), one of the most relevant quantitative sensory testing markers for central sensitization; a high frequency of NK cells correlated with low MPS. The analysis of the individual follow-up showed a worsening of the pain condition if NK-cell frequency was low. Low NK-cell frequency is associated with signs of central sensitization (MPS), whereas high NK-cell frequency might prevent central sensitization. Therefore, NK cells seem to play a protective role within the neuroinflammatory cascade and may be used as a marker for pain chronicity.

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Persistence of a T Cell Infiltrate in Human Ganglia Years After Herpes Zoster and During Post-herpetic Neuralgia

Cited by 10 publications

References 31 publications

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

Long-term two-photon imaging of spinal cord in freely behaving mice

Protective role of natural killer cells in neuropathic pain conditions

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