Lymph Node Cellular Dynamics in Cancer and HIV: What Can We Learn for the Follicular CD4 (Tfh) Cells?

Poultsidi, Antigoni; Dimopoulos, Yiannis; He, Ting-Fang; Chavakis, Triantafyllos; Saloustros, Emmanouil; Lee, Peter P.; Petrovas, Constantinos

doi:10.3389/fimmu.2018.02233

Cited by 11 publications

(9 citation statements)

References 178 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we found a decrease in the proportion of MoMDSCs in SN, which might promote T cell immunity through various metabolic effects [ 27 ]. Meanwhile, an increase in Tfh cells in SN could enhance antitumor immunity [ 28 ]. Here, we observed that in SN, M2 macrophages, a type of immunosuppressive cells, were clustered in subcapsular sinus areas of lymph nodes, the main functional area for antigen presentation [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients

Tang

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

Purpose. This study is aimed at immunologically characterizing sentinel lymph nodes (SNs) in colorectal cancer (CRC) patients and identifying changes in immunological phenotype and function of SNs isolated from the tumor immunosuppressive microenvironment. Methods. A total of 53 pairs of matched SNs and non-SNs (NSNs) were collected by using a lymph node tracer dye. Flow cytometry was performed to detect the immunophenotype of T cells as well as the expression of activation and inhibitory markers. Differential expression and distribution of characteristic immune cell markers were analyzed by multiplex immunohistochemistry (mIHC). Transcriptomics analysis was conducted to compare the differences in the expression of immune-related genes among lymph nodes. The ex vivo culture of lymph nodes was carried out to examine changes in immunological phenotypes and functions. Results. Compared with NSNs, SNs harbored a significantly higher percentage of regulatory T cells (Tregs) but a lower proportion of MoMDSCs. As indicated in the mIHC assays, Tregs, T follicular helper (Tfh) cells, and M2 macrophages were mainly distributed in cortical areas, germinal centers, and subcapsular sinus areas, respectively, while significantly higher numbers of Tregs and Tfh cells were detected in SNs as compared to NSNs. Moreover, GSEA revealed that T cell activation genes and CD8+ T cell exhaustion-related genes are enriched in SNs and NSNs, respectively. The ex vivo culture led to an increase in the proportion of CD4+ cells, while activating T cells in SNs. In addition, SNs displayed a higher increase in the expression of cytokines IFN-γ, TNF-α, and sFas than NSNs. Conclusion. SNs are shown to be in an immune active state in vivo, while highly expressing inhibitory cytokines and suppressive markers. The ex vivo culture enhanced antitumor immunological function of SN-T cells, providing a starting material for adoptive cell therapy for CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients

Tang

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…Decreased adaptive immune responses are a hallmark of progressive lentiviral infection (27)(28)(29)(30)(31)(32)(33). Although the underlying mechanisms are multifactorial, preferential HIV/SIV infection of follicle-resident CD4 ϩ Tfh cells (reviewed in reference 65), loss of pathogen-specific memory CD4 ϩ T cells (66,67), exhaustion of adaptive lymphocytes (68,69), and aberrant inflammation (70) are all described contributors.…”

Section: Discussionmentioning

confidence: 99%

“…Tfh cells are an important reservoir for HIV/SIV (27)(28)(29)(30)(31)(32)(33), and their predicted infection by SIV in our coinfection model may compromise the generation of ZIKV antibodies. A combination of Tfh loss and ISG-mediated hypoantigenemia may be cumulatively operative in decreasing ZIKV-specific NAbs.…”

Section: Discussionmentioning

confidence: 99%

“…While this sensitivity to opportunistic infections generally occurs very late after the acquisition of infection, several studies have shown that HIV-infected individuals and SIV-infected rhesus macaques (RMs) mount suboptimal adaptive immune responses to vaccination and viral infections (24)(25)(26)(27). The decreased humoral responses to vaccination, in particular, have been attributed to preferential infection of lymph node follicle-resident T follicular cells, which provide critical help to B cells during the germinal center reaction (27)(28)(29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

Vinton

Magaziner

Dowd

et al. 2019

mBio

View full text Add to dashboard Cite

Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1-to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIVpositive (SIV ϩ ) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV ϩ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV ϩ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIVinfected individuals influence ZIKV infection.

show abstract

“…In NK cells from HIV infected individuals, expression of TIGIT is correlated with disease progression and NK cell dysfunction (160). Although the role of TIGIT is not well-defined in HIV infection, TIGIT ligands such as PVR are increased by CD4 T FH cells in lymph nodes from HIV infected patients compared to heathy donors suggesting it may play a role in viral persistence (161).…”

Section: Tigit Expression In Hiv Infectionmentioning

confidence: 99%

The Role of Immunomodulatory Receptors in the Pathogenesis of HIV Infection: A Therapeutic Opportunity for HIV Cure?

2020

View full text Add to dashboard Cite

Immune activation is the hallmark of HIV infection and plays a role in the pathogenesis of the disease. In the context of suppressed HIV RNA replication by combination antiretroviral therapy (cART), there remains immune activation which is associated to the HIV reservoirs. Persistent virus contributes to a sustained inflammatory environment promoting accumulation of "activated/exhausted" T cells with diminished effector function. These T cells show increased expression of immunomodulatory receptors including Programmed cell death protein (PD1), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA4), Lymphocyte activation gene 3 (LAG3), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain containing 3 (TIM3) among others. More importantly, recent reports had demonstrated that, HIV infected T cells express checkpoint receptors, contributing to their survival and promoting maintenance of the viral reservoir. Therapeutic strategies are focused on viral reservoir elimination and/or those to achieve sustained cART-free virologic remission. In this review, we will discuss the immunological basis and the latest advances of the use of checkpoint inhibitors to treat HIV infection.

show abstract

Lymph Node Cellular Dynamics in Cancer and HIV: What Can We Learn for the Follicular CD4 (Tfh) Cells?

Cited by 11 publications

References 178 publications

Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients

Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients

Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

The Role of Immunomodulatory Receptors in the Pathogenesis of HIV Infection: A Therapeutic Opportunity for HIV Cure?

Contact Info

Product

Resources

About