The Role of PD-1 in Acute and Chronic Infection

Jubel, Jil M; Barbati, Zachary R.; Burger, C.; Wirtz, Dieter Christian; Schildberg, Frank A.

doi:10.3389/fimmu.2020.00487

Cited by 212 publications

(213 citation statements)

References 126 publications

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“…However, its expression is induced by T cell receptor (TCR) activation (27) and TCR downstream NFAT signaling (28). PD-1 expression is a hallmark of recent TCR-based recognition of MHC-presented antigens that is often up-regulated on cytotoxic effector T cells during acute infections (29,30). We found that about 20% of total CD8+ T cells expressed PD-1 in healthy controls, as well as in COVID-19 patients (Fig.…”

Section: Expansion Of Cd8+ T Cells With a Cytotoxic Profile Upon Sarsmentioning

confidence: 82%

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Westmeier

Paniskaki

Karaköse

et al. 2020

Preprint

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SARS-CoV-2 infection induces a T cell response that most likely contributes to virus control in COVID-19 patients, but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients.Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B, as well as perforin within different effector CD8+ T cell subsets. PD-1 expressing CD8+ T cells also produced cytotoxic molecules during acute infection indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2.Our data provides valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.ImportanceCytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients.

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Section: Expansion Of Cd8+ T Cells With a Cytotoxic Profile Upon Sarsmentioning

confidence: 82%

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Westmeier

Paniskaki

Karaköse

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…We also analyzed the T-cell exhaustion markers TIGIT, PD-L1, PD1 and TIM3. Notably, PD1 and TIM3, while often classified as exhaustion markers, have also been shown to be activated during other acute infections (34,35). Finally, we stained for CD27 and CD28 as loss of these markers has been found to represent a loss of differentiated memory T cells, suggesting a more senescent phenotype (36).…”

Section: Immune Dysregulation In Hospitalized and Non-hospitalized Samentioning

confidence: 93%

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Files¹,

Boppana²,

Perez³

et al. 2021

Journal of Clinical Investigation

124

108

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SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, OX40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

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“…One of the causes of antitumor response inhibition is the expression of immune checkpoints (ICPs). In normal conditions, ICPs are essential for the maintenance of tolerance towards self-antigens [ 40 , 41 ]. However, in pathological conditions, including OC, ICPs such as PD-1 and its ligand PD-L1/PD-L2 become negative regulators that may inhibit T cell functions and mediate in cancer immune escape from immune system surveillance [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer

Wertel

Suszczyk

Pawłowska

et al. 2020

Journal of Immunology Research

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Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.

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The Role of PD-1 in Acute and Chronic Infection

Cited by 212 publications

References 126 publications

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer

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The Role of PD-1 in Acute and Chronic Infection

Cited by 212 publications

References 126 publications

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer

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Prognostic and Clinical Value of Interleukin 6 and CD45⁺CD14⁺ Inflammatory Cells with PD-L1⁺/PD-L2⁺ Expression in Patients with Different Manifestation of Ovarian Cancer