The Lymph Node in HIV Pathogenesis

Dimopoulos, Yiannis; Moysi, Eirini; Petrovas, Constantinos

doi:10.1007/s11904-017-0359-7

Cited by 32 publications

(34 citation statements)

References 90 publications

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“…These results demonstrate that hetIL-15 treatment can facilitate localization of GrzB + CD8 + T cells in follicles in both uninfected and SHIV + macaques. Therefore, hetIL-15 treatment increases the number of GrzB + lymphocytes not only in peripheral effector sites, but also in LN follicles, a well-documented sanctuary site for HIV/SIV [ 35 – 40 , 64 ]. This increase in GrzB + CD8 + cell numbers in B cell follicles raised the possibility that productively infected cells within follicles may become more accessible to immune surveillance.…”

Section: Resultsmentioning

confidence: 99%

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

Watson¹,

Moysi²,

Valentı́n³

et al. 2018

PLoS Pathog

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B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry) of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals.Trial registration: ClinicalTrials.gov NCT02452268

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Section: Resultsmentioning

confidence: 99%

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

Watson¹,

Moysi²,

Valentı́n³

et al. 2018

PLoS Pathog

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“…CXCR5 + CD8 + T cells mainly exist in lymphoid tissues and exhibited strong HIV-specific CTL function. In addition, lymphoid tissue is an important site for HIV replication ( 35 ). This may be the reason of negative correlation between CXCR5 + CD8 + T cells and HIV disease progression.…”

Section: Discussionmentioning

confidence: 99%

Dichotomous Roles of Programmed Cell Death 1 on HIV-Specific CXCR5+ and CXCR5− CD8+ T Cells during Chronic HIV Infection

et al. 2017

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BackgroundCXCR5+CD8+ T cells have been demonstrated to play an important role in the control of chronic viral replication; however, the relationship between CXCR5+CD8+ T cells, HIV disease progression, and programmed cell death 1 (PD-1) expression profile on CXCR5+CD8+ T cells during HIV infection remain poorly understood.MethodsWe enrolled a total of 101 HIV patients, including 62 typical progressors, 26 complete responders (CRs), and 13 immune non-responders (INRs). Flow cytometric analysis, immunohistochemical staining, and relative function (i.e., cytokine secretion and PD-1 blockade) assays were performed to analyze the properties of CXCR5+CD8+ T cells.ResultsHIV-specific CXCR5+CD8+ T cells in the peripheral blood and distribution of CXCR5+CD8+ T cells in the lymph node (LN) were negatively correlated with disease progression during chronic HIV infection. PD-1 was highly expressed on CXCR5+CD8+ T cells and positively associated with peripheral CD4+ T cell counts. Functionally, IFN-γ and TNF-α production of CXCR5+CD8+ T cells were reduced by PD-1 pathway blockade, but the production of IFN-γ and TNF-α from CXCR5−CD8+ T cells increased in response to TCR stimulation. Interestingly, PD-1 expression was constantly retained on CXCR5+CD8+ T cells while significantly decreased on CXCR5−CD8+ T cells after successful antiretroviral treatment in chronic HIV-infected patients.ConclusionPD-1+CXCR5+CD8+ T cells are functional cytotoxic T cells during chronic HIV infection. PD-1+CXCR5+CD8+ T cells may represent a novel therapeutic strategy for the disease.

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“…Cervical lymph nodes like other LNs play a central role in the development of adaptive immunity against pathogens and, particularly, the generation of antigen-specific B cell responses in specialized areas within GCs ( 82 ). Very early in the HIV epidemic, LN pathology was recognized as an important consequence of HIV infection since the beginning of the epidemic.…”

Section: Key Cellular Players In the Clnmentioning

confidence: 99%

Follicular Dendritic Cells of Lymph Nodes as Human Immunodeficiency Virus/Simian Immunodeficiency Virus Reservoirs and Insights on Cervical Lymph Node

2018

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A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART). Besides prolonged virion retention on FDCs in LNs and CLNs, the suboptimal penetration of cART at these anatomical sites is another factor contributing to establishing and maintaining this viral reservoir. Unlike the FDCs within the peripheral LNs, the CLN FDCs have only recently garnered attention. This interest in CLN FDCs has been driven by detailed characterization of the meningeal lymphatic system. As the CSF drains through the meningeal lymphatics and nasal lymphatics via the cribriform plate, CLN FDCs may acquire HIV after capturing them from T cells, antigen-presenting cells, or cell-free virions. In addition, CD4+ T follicular helper cells within the CLNs are productively infected as a result of acquiring the virus from the FDCs. In this review, we outline the underlying mechanisms of viral accumulation on CLN FDCs and its potential impact on viral resurgence or achieving a cure for HIV infection.

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The Lymph Node in HIV Pathogenesis

Cited by 32 publications

References 90 publications

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

Dichotomous Roles of Programmed Cell Death 1 on HIV-Specific CXCR5+ and CXCR5− CD8+ T Cells during Chronic HIV Infection

Follicular Dendritic Cells of Lymph Nodes as Human Immunodeficiency Virus/Simian Immunodeficiency Virus Reservoirs and Insights on Cervical Lymph Node

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