Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques

Enyindah-Asonye, Gospel; Nwankwo, Anthony; Rahman, Mohammad Arif; Hunegnaw, Ruth; Hogge, Christopher James; Hait, Sabrina Helmold; Ko, Eunju; Hoang, Tanya; Robert-Guroff, Marjorie

doi:10.3389/fimmu.2019.03005

Cited by 4 publications

(4 citation statements)

References 49 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pulmonary CD4 + T cells from dysbiotic newborns coexpressed T cell immunoglobulin and mucin-domain containing-3 (TIM-3) and lymphocyte activating gene-3 (LAG-3), which are markers linked to T cell exhaustion (fig. S8A) ( 31 , 77 ). The frequency of dysfunctional CD4 + T cells (expressing LAG-3) correlated with disease severity (Fig.…”

Section: Resultsmentioning

confidence: 99%

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota

et al. 2022

View full text Add to dashboard Cite

Although modern clinical practices such as cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum antibiotics alters intestinal microbiota and causes dysbiosis. Infants exposed to perinatal antibiotics have an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how the gut microbiota sculpt pulmonary immune responses, promoting recovery and resolution of infection in newborn rhesus macaques. Early-life antibiotic exposure interrupted the maturation of intestinal commensal bacteria and disrupted the developmental trajectory of the pulmonary immune system, as assessed by single-cell proteomic and transcriptomic analyses. Early-life antibiotic exposure rendered newborn macaques more susceptible to bacterial pneumonia, concurrent with increases in neutrophil senescence and hyperinflammation, broad inflammatory cytokine signaling, and macrophage dysfunction. This pathogenic reprogramming of pulmonary immunity was further reflected by a hyperinflammatory signature in all pulmonary immune cell subsets coupled with a global loss of tissue-protective, homeostatic pathways in the lungs of dysbiotic newborns. Fecal microbiota transfer was associated with partial correction of the broad immune maladaptations and protection against severe pneumonia. These data demonstrate the importance of intestinal microbiota in programming pulmonary immunity and support the idea that gut microbiota promote the balance between pathways driving tissue repair and inflammatory responses associated with clinical recovery from infection in infants. Our results highlight a potential role for microbial transfer for immune support in these at-risk infants.

show abstract

Section: Resultsmentioning

confidence: 99%

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota

et al. 2022

View full text Add to dashboard Cite

show abstract

“…More recently, in SIV-infected macaques, the expression of CD6 by PD-1 + CD8 T cells was associated with a reduced proliferation, cytokine secretion and cytotoxic capacity when compared to their CD6 − counterpart. The frequency of CD6 + PD-1 + CD8 T cells positively correlated with SIV viral load and combined targeting of CD6 and PD-1 effectively restored the CD8 T cell proliferation capacity in vitro , suggesting that CD6 may be a new immunotherapeutic target ( 72 ).…”

Section: Hallmarks Of T Cell Exhaustion In Hiv-1 Infectionmentioning

confidence: 99%

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure

et al. 2020

View full text Add to dashboard Cite

The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the establishment of chronic pathologies. Prototypical examples of immune system defeat are cancer and Human Immunodeficiency Virus-1 (HIV-1) infection. In both conditions, the immune system is persistently exposed to antigens leading to systemic inflammation, lack of generation of long-term memory and exhaustion of effector cells. This triggers a negative feedback loop where effector cells are unable to resolve the pathology and cannot be replaced due to the lack of a pool of undifferentiated, self-renewing memory T cells. In addition, in an attempt to reduce tissue damage due to chronic inflammation, antigen presenting cells and myeloid components of the immune system activate systemic regulatory and tolerogenic programs. Beside these homologies shared between cancer and HIV-1 infection, the immune system can be shaped differently depending on the type and distribution of the eliciting antigens with ultimate consequences at the phenotypic and functional level of immune exhaustion. T cell differentiation, functionality, cytotoxic potential and proliferation reserve, immune-cell polarization, upregulation of negative regulators (immune checkpoint molecules) are indeed directly linked to the quantitative and qualitative differences in priming and recalling conditions. Better understanding of distinct mechanisms and functional consequences underlying disease-specific immune cell dysfunction will contribute to further improve and personalize immunotherapy. In the present review, we describe relevant players of immune cell exhaustion in cancer and HIV-1 infection, and enumerate the best-defined hallmarks of T cell dysfunction. Moreover, we highlight shared and divergent aspects of T cell exhaustion and T cell activation to the best of current knowledge.

show abstract

“…[33] BAL T cells show an exhausted phenotype, which is associated with high viral replication, chronic inflammation, and severe depletion of tissueresident CD4+ T cells, driving some of the HIV-1 associated lung complications. [34,35] Interestingly, during chronic HIV-1 infection, T cell profiles and dynamics differ significantly between BAL and blood, suggesting concordant and discordant immune responses in different body sites. [36][37][38][39] Tumor growth during HIV-1-associated pKS in the lung mucosa most likely affects the local immune environment.…”

Section: Introductionmentioning

confidence: 99%

“…Investigations of this mucosal site in HIV-1 infected individuals by bronchoscopy revealed that chronic HIV-1 infection causes inflammatory alveolitis by infiltration of T cells from the circulation into the alveolar space [33] . BAL T cells show an exhausted phenotype, which is associated with high viral replication, chronic inflammation, and severe depletion of tissue-resident CD4+ T cells, driving some of the HIV-1 associated lung complications [34,35] . Interestingly, during chronic HIV-1 infection, T cell profiles and dynamics differ significantly between BAL and blood, suggesting concordant and discordant immune responses in different body sites [36–39] .…”

Section: Introductionmentioning

confidence: 99%

Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma

et al. 2021

View full text Add to dashboard Cite

Pulmonary Kaposi sarcoma (pKS) caused by Human herpesvirus 8 (HHV-8) is a devastating form of KS in patients with advanced acquired immunodeficiency syndrome (AIDS) and is associated with increased morbidity and mortality. Blood T cells play a central role in the response of HIV-1 and HHV-8. However, little information is available on T cells in the alveolar space of HIV-1-associated pKS patients. Therefore, we examined CD8+ and CD4+ T cells in the alveolar space in comparison with the blood of patients with pKS. We recruited 26 HIV-1 positive patients with KS, including 15 patients with pKS. Bronchoalveolar lavage (BAL) cells and blood mononuclear cells were analyzed for T cell memory phenotypes, surface markers associated with exhaustion, and intracellular cytokine staining (ICS) using flow cytometry. HIV-1 and HHV-8 viral loads were measured in plasma by quantitative PCR. BAL T cells showed reduced inflammatory capacities and significantly diminished polyfunctionality compared to blood T cells from patients with pKS. This was not accompanied by increased expression of exhaustion markers, such as TIM-3 and PD-1. More importantly, we found a negative correlation between the production of MIP1-β and TNF-α in T cells in BAL and blood, indicating compartmentalised immune responses to pKS and accentuated chronic HIV-1/HHV-8 pathogenesis via T cells in the lungs of people with pKS.

show abstract

Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques

Cited by 4 publications

References 49 publications

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure

Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma

Contact Info

Product

Resources

About