Long-Term Presence of Virus-Specific Plasma Cells in Sensory Ganglia and Spinal Cord following Intravaginal Inoculation of Herpes Simplex Virus Type 2

Milligan, Gregg N.; Meador, Michael G.; Chu, Chin-Fun; Young, Christal G.; Martin, Talitha L.; Bourne, Nigel

doi:10.1128/jvi.79.17.11537-11540.2005

Cited by 17 publications

(14 citation statements)

References 28 publications

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“…This, in turn, might result in limitation in the amount of virus establishing latency and reduction in recurrent lesions at the original site of infection, thus impacting the transmission of virus to new hosts, including neonates. The results of the present study demonstrate that HSV-specific CD4 ϩ T cells are recruited to HSV-infected sensory ganglia, where they are maintained long after viral infection, along with HSV-specific CD8 ϩ T cells (32) and plasma cells (43). Our findings further demonstrate an important role for these CD4 ϩ T cells in protection of the sensory ganglia and spinal cord and suggest that an effective HSV vaccine may need to elicit immune responses at both the site of epithelial infection and in the neural tissues.…”

Section: Discussionmentioning

confidence: 81%

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

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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

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Section: Discussionmentioning

confidence: 81%

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

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“…HSV-specific IgA, IgG, IgG1 and IgG2 titers from immune serum or ASC culture supernatants were obtained by ELISA as performed previously [28] . Plate-bound immunoglobulins were detected by addition of polyclonal goat anti-guinea pig IgG (#A60-110A) or polyclonal rabbit anti-guinea pig IgA (#A60-105) (Bethyl Laboratories, Inc., Montgomery, TX) followed by polyclonal HRP-rabbit anti-goat IgG (#A50-100P) or polyclonal HRP-goat anti-rabbit IgG (#A120-101P; Bethyl laboratories, Inc., Montgomery, TX), respectively.…”

Section: Methodsmentioning

confidence: 99%

Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs

et al. 2014

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Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbosacral sensory ganglia, and spinal cord of previously-infected animals. Memory B cells were detected primarily in the spleen and to a lesser extent in bone marrow but not in the genital tract or neural tissues suggesting that the HSV-specific antibody-secreting cells present at peripheral sites of HSV-2 infection represented persisting populations of plasma cells. The antibody produced by these cells isolated from neural tissues of infected animals was functionally relevant and included antibodies specific for HSV-2 glycoproteins and HSV-2 neutralizing antibodies. A vigorous IFN-γ-secreting T cell response developed in the spleen as well as the sites of HSV-2 infection in the genital tract, lumbosacral ganglia and spinal cord following acute HSV-2 infection. Additionally, populations of HSV-specific tissue-resident memory T cells were maintained at these sites and were readily detected up to 150 days post HSV-2 infection. Unlike the persisting plasma cells, HSV-specific memory T cells were also detected in uterine tissue and cervicothoracic region of the spinal cord and at low levels in the cervicothoracic ganglia. Both HSV-specific CD4+ and CD8+ resident memory cell subsets were maintained long-term in the genital tract and sensory ganglia/spinal cord following HSV-2 infection. Together these data demonstrate the long-term maintenance of both humoral and cellular arms of the adaptive immune response at the sites of HSV-2 latency and virus shedding and highlight the utility of the guinea pig infection model to investigate tissue-resident memory in the setting of HSV-2 latency and spontaneous reactivation.

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“…We recently developed assays to detect and quantify HSV-specific antibody secreting cells in lymphoid and peripheral tissues of HSV-2 infected guinea pigs (Milligan et al, 2005; Xia et al, 2014). Cell-mediated responses have been assessed previously in other immunization systems as the antigen-specific proliferation of lymphocyte populations from immune animals through the use of 3 H thymidine uptake assays (Cho and McMurray, 2007) or MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) dye-based proliferation assays (Nanda et al, 2014; Terhuja et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection

Perry

Banasik

Gorder

et al. 2016

Journal of Immunological Methods

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Genital infections with herpes simplex virus type 2 (HSV-2) are a source of considerable morbidity and are a health concern for newborns exposed to virus during vaginal delivery. Additionally, HSV-2 infection diminishes the integrity of the vaginal epithelium resulting in increased susceptibility of individuals to infection with other sexually transmitted pathogens. Understanding immune protection against HSV-2 primary infection and immune modulation of virus shedding events following reactivation of the virus from latency is important for the development of effective prophylactic and therapeutic vaccines. Although the murine model of HSV-2 infection is useful for understanding immunity following immunization, it is limited by the lack of spontaneous reactivation of HSV-2 from latency. Genital infection of guinea pigs with HSV-2 accurately models the disease of humans including the spontaneous reactivation of HSV-2 from latency and provides a unique opportunity to examine virus-host interactions during latency. Although the guinea pig represents an accurate model of many human infections, relatively few reagents are available to study the immunological response to infection. To analyze the cell-mediated immune response of guinea pigs at extended periods of time after establishment of HSV-2 latency, we have modified flow-cytometry based proliferation assays and IFN-γ ELISPOT assays to detect and quantify HSV-specific cell-mediated responses during latent infection of guinea pigs. Here we demonstrate that a combination of proliferation and ELISPOT assays can be used to quantify and characterize effecter function of virus-specific immune memory responses during HSV-latency.

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Long-Term Presence of Virus-Specific Plasma Cells in Sensory Ganglia and Spinal Cord following Intravaginal Inoculation of Herpes Simplex Virus Type 2

Cited by 17 publications

References 28 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

Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs

Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection

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Long-Term Presence of Virus-Specific Plasma Cells in Sensory Ganglia and Spinal Cord following Intravaginal Inoculation of Herpes Simplex Virus Type 2

Cited by 17 publications

References 28 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

Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs

Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection

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Product

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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