T‐cell exhaustion in HIV infection

Fenwick, Craig; Joo, Victor; Jacquier, Patricia; Noto, Alessandra; Banga, Riddhima; Perreau, Matthieu; Pantaleo, Giuseppe

doi:10.1111/imr.12823

Cited by 286 publications

(265 citation statements)

References 143 publications

Supporting

Mentioning

249

Contrasting

Unclassified

Order By: Relevance

“…T cell activation is typically observed during acute viral infections (73)(74)(75), and, as expected (10, 13), we observed increased activation of both CD4 + and CD8 + T cells in severe COVID-19. Eighteen of twenty of the top phenotypic parameters distinctive of severe COVID-19 were related to T cell activation.…”

Section: Discussionsupporting

confidence: 90%

Comprehensive mapping of immune perturbations associated with severe COVID-19

Kuri-Cervantes

Pampena

Meng³

et al. 2020

View full text Add to dashboard Cite

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

show abstract

Section: Discussionsupporting

confidence: 90%

Comprehensive mapping of immune perturbations associated with severe COVID-19

Kuri-Cervantes

Pampena

Meng³

et al. 2020

View full text Add to dashboard Cite

show abstract

“…T cell activation is typically observed during acute viral infections (58)(59)(60), and as expected (15,18) we observed increased activation of both CD4+ and CD8+ T cells in severe COVID-19 that correlated with the plasmablast frequency. However, T cell activation was very heterogeneous across the severe COVID-19 patients, being equivalent to baseline in some while reaching up to ~25% of memory CD8+ T cells in others.…”

Section: Modulation Of Innate Immune Cells Manifested In a Number Of supporting

confidence: 86%

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Kuri-Cervantes

Pampena

Meng

et al. 2020

Preprint

View full text Add to dashboard Cite

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals.We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.One Sentence Summary: Broad immune perturbations in severe COVID-19 surrogates, as well as the medical personnel in charge of patient care.

show abstract

“…At the same time, CD4 + helper T cells (Th) can assist cytotoxic T cells and B cells and enhance their ability to clear pathogen (14). However, persistent stimulation by the virus may induce T cell exhaustion, leading to loss of cytokine production and reduced function (15,16). Earlier studies have been unclear regarding the numbers and function of T cells in COVID-19 patients, albeit with suggestions of depressed lymphocyte counts (4,6).…”

Section: Discussionmentioning

confidence: 99%

Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

et al. 2020

View full text Add to dashboard Cite

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4 + and CD8 + T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8 + T cells or CD4 + T cells lower than 800, 300, or 400/µL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/µL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.

show abstract

T‐cell exhaustion in HIV infection

Cited by 286 publications

References 143 publications

Comprehensive mapping of immune perturbations associated with severe COVID-19

Comprehensive mapping of immune perturbations associated with severe COVID-19

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Contact Info

Product

Resources

About