scholarly journals Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2239
Author(s):  
Allison E. Kennedy ◽  
Laura Cook ◽  
Jessica A. Breznik ◽  
Braeden Cowbrough ◽  
Jessica G. Wallace ◽  
...  
Keyword(s):  
T Cells ◽  
Symptom Onset ◽  
Post Infection ◽  
Chemokine Receptors ◽  
Respiratory Infections ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Circulating T Cells ◽  
And Function ◽  
Cellular Immune

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1–3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6–9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1–3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6–9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.

scholarly journals Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections

2021 ◽  
Author(s):  
Allison E. Kennedy ◽  
Laura Cook ◽  
Jessica A. Breznik ◽  
Braeden Cowbrough ◽  
Jessica G. Wallace ◽  
...  
Keyword(s):  
T Cells ◽  
Symptom Onset ◽  
Post Infection ◽  
Chemokine Receptors ◽  
Respiratory Infections ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Circulating T Cells ◽  
And Function ◽  
Cellular Immune

AbstractSurvivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n=22) compared to those that had recovered from other mild respiratory infections (n=11). Individuals who had mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, polyclonal activation of T cells was higher in individuals who had recently experienced a mild SARS-CoV-2 infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for up to three months after mild or asymptomatic SARS-CoV-2 infections.

scholarly journals Expression patterns of chemokine receptors on circulating T cells from myelodysplastic syndrome patients

2013 ◽  
Vol 2 (2) ◽  
pp. e23138 ◽  
Author(s):  
Kristoffer Evebø Sand ◽  
Kristin Paulsen Rye ◽  
Bård Mannsåker ◽  
Øystein Bruserud ◽  
Astrid Olsnes Kittang
Keyword(s):  
T Cells ◽  
Myelodysplastic Syndrome ◽  
Chemokine Receptors ◽  
Expression Patterns ◽  
Circulating T Cells

The Role of IL-12 and IL-23 in the Generation and Maintenance of Memory CD4+ T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2664-2664
Author(s):  
Aileen M. Cleary ◽  
David B. Lewis
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Chemokine Receptors ◽  
Human Memory ◽  
Surface Expression ◽  
Effector Memory ◽  
Memory Cells ◽  
Peripheral Lymph ◽  
And Function ◽  
Memory Cd4 T Cells

Abstract Human memory CD4+ T cells can be distinguished from antigenically-naïve CD4+ T cells based on their CD45RAlowCD45R0high and CD45RAhighCD45R0low surface phenotypes, respectively. Memory CD4+ T cells from adult peripheral blood can be further divided based on surface expression of the CCR7 chemokine receptor. Th1 memory CD4+ T cells that are CCR7high (putative central memory cells or Tcm) are expected to be preferentially targeted to peripheral lymph nodes where the ligands for CCR7 are expressed in high amounts. These cells have been reported to lack expression of the CCR3 and CCR5 chemokine receptors, which facilitate entry into inflamed tissues, and produce little or no interferon (IFN)-γ after stimulation via the αβ-TCR/CD3 complex. CD45RAlowCD45R0highCCR7low CD4+ T cells account for virtually all IFN-g production by human CD4 T cells after ab-TCR/CD3 stimulation using monoclonal antibodies, and for this reason were termed effector memory cells (Tem). These findings, as well as the observation of shorter telomere lengths for memory CD4+ T cells that are CCR7low compared to those that CCR7high suggest that the Tcm population may be an intermediate between naïve CD4+ T cells and Tem. It has recently been proposed that the level of signal strength and γc containing cytokines play a role in memory T cell generation. However, little is known whether IL-12 or IL-23 are necessary and for this differentiation and/or maintenance. Our laboratory has previously described a patient with IL-12Rβ1 deficiency, which ablates both IL-12 and IL-23 signaling. This patient had a deficiency in Tem number and function, unexpectedly suggesting that IL-12 and/or IL-23 may play a key role in this process. We therefore hypothesized that signaling through IL-12Rβ1 plays a key role in the latter stages of generation and/or maintenance of human memory CD4+ T cells. Preliminary data thus far show CCR7 expression to be slightly decreased on activated Tcm in response to incubation with IL-2 or IL-12 alone, and to a greater extent with IL-2 and IL-12 incubated together. In addition, spontaneous apoptosis of both Tcm and Tem is decreased upon incubation with IL-12. Taken together, these data suggest that IL-12 may play a role in both generation of Tem and maintenance of both Tcm and Tem.

scholarly journals The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies

2015 ◽  
Vol 5 (4) ◽  
pp. e306-e306 ◽  
Author(s):  
T Dosani ◽  
M Carlsten ◽  
I Maric ◽  
O Landgren
Keyword(s):  
T Cells ◽  
Immune System ◽  
Natural Killer ◽  
Γδ T Cells ◽  
Tumor Evolution ◽  
The Status ◽  
And Function ◽  
Cellular Immune ◽  
Functional Profiles ◽  
Killer T Cells

Abstract As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, γδ T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions.

Circulating T cells derived from acute leukemia patients with severe therapy-induced cytopenia express a wide range of chemokine receptors

Hematology ◽  
2008 ◽  
Vol 13 (6) ◽  
pp. 329-332 ◽  
Author(s):  
Astrid Marta Olsnes ◽  
Elisabeth Ersvær ◽  
Anita Ryningen ◽  
Øystein Bruserud
Keyword(s):  
T Cells ◽  
Acute Leukemia ◽  
Chemokine Receptors ◽  
Wide Range ◽  
Circulating T Cells

C-Reactive Protein Binds to FcγRII and Impairs the Differentiation and Function of Dendritic Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1276-1276
Author(s):  
Jianfei Qian ◽  
Jing Yang ◽  
Siqing Wang ◽  
Liang Zhang ◽  
Sungyoul Hong ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Soluble Antigen ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Tnf Α ◽  
And Function

Abstract Human C-reactive protein (CRP) is an acute-phase protein, and elevated levels of CRP are present in patients with infections, inflammatory diseases, necrosis such as myocardial infarction, or malignancies including multiple myeloma (MM), lymphoma, and carcinoma. CRP has many biological functions and is involved in host defense, regulation of inflammation, and modulation of autoimmune diseases. Although our current understanding of CRP interaction with complement and Fcγ receptors (FcγR) has elucidated a regulatory role of CRP in these disease situations, it is not clear whether CRP affects the function of immune cells such as dendritic cells (DCs). In this study, we investigated the effect of CRP on DC differentiation, maturation, and function. CD14+ monocytes isolated from human peripheral blood mononuclear cells were cultured in RPMI-1640 medium supplemented with GM-CSF and IL-4 for 5 days to generate immature DCs (imDCs), and were further treated with IL-1β and TNF-α for 2 additional days to produce mature DCs (mDCs). CRP (5–100 μg/mL) was added to the cultures during DC differentiation (on days 0 and 3) or maturation (on day 5). The presence of CRP in cultures reduced imDC cell yields in a dose-dependent manner. Significantly lower cell yields were detected in cultures with 5 to 10 μg/mL CRP. Compared with untreated controls, CRP treatment (10 μg/mL) led to inhibited surface expression of DC-related molecules HLA-ABC, CD1a, CD40, and CD54; increased secretion of IL-6, IL-8, and IL-10; reduced production of TGF-β by imDCs; and decreased secretion of IL-12 by mDCs. Furthermore, the function of CRP-treated DCs was also impaired, evident by the markedly decreased ability of imDCs to phagocytose apoptotic cells and to uptake and present soluble antigen to antigen-specific T cells. Compared with untreated controls, CRP-treated mDCs had reduced capacity at activating allospecific T cells, which consequently secreted significantly lower amounts of IFN-γ, IL-2, and TNF-α compared with T cells activated by normal mDCs. Western blot analysis showed that CRP treatment led to inhibited phosphorylation of ERK and p38 MAPKs, and inhibited NFκB activity in the differentiating cells. Monocytes and DCs all express FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16), and the expression of FcγRII, but not FcγRI and FcγRIII, were upregulated on CRP-treated DCs. The detrimental effects of CRP on DCs were abrogated by blocking antibody against CRP and by antibody against FcγRII, but not against FcγRI or FcγRIII. These results indicate that CRP affected DC differentiation via binding to cell surface FcγRII. Taken together, this study demonstrates for the first time that CRP at high concentrations has detrimental effects on in vitro differentiation and function of DCs. Further studies will be needed to examine the clinical and biological relevance of this observation.

scholarly journals Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Science ◽  
2021 ◽  
pp. eabf4063
Author(s):  
Jennifer M. Dan ◽  
Jose Mateus ◽  
Yu Kato ◽  
Kathryn M. Hastie ◽  
Esther Dawen Yu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Symptom Onset ◽  
Post Infection ◽  
Memory B Cells ◽  
Spike Protein ◽  
T Cell Memory ◽  
Immune Memory ◽  
Specific Memory

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

scholarly journals Metabolic and functional impairment of CD8+ T cells from the lungs of influenza-infected obese mice

2020 ◽  
Author(s):  
William D. Green ◽  
Abrar E. Al-Shaer ◽  
Qing Shi ◽  
Nancie J MacIver ◽  
Melinda A. Beck ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Post Infection ◽  
Cytokine Production ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Obese Mice ◽  
Diet Induced Obesity ◽  
And Function

ABSTRACTBackgroundObesity increases influenza disease risk in millions of adults worldwide. In this study, we investigated the effect of diet-induced obesity on pulmonary CD8+ T cell metabolism and function as a mechanism of impairment.MethodsMale C57BL/6J mice were fed either control (10% kcal/g) or high-fat (60% kcal/g) diet. Sub-lethal A/PR/8/34 influenza virus infection generated a robust pulmonary immune response. T cell metabolism and function were assessed at day 10 and day 24 post infection.ResultsAt day 10 post infection, CD8+ T cells from obese mice had impaired oxidative and glycolytic metabolism, greater fatty acid uptake, and decreased effector populations and cytokine production. At infection resolution, obese mice had lower numbers of naïve and central memory CD8+ T cell populations in the lungs.ConclusionDiet-induced obesity increases influenza virus pathogenesis through CD8+ T cell mediated metabolic reprogramming resulting in suppressed effector CD8+ T cell function.SummaryDiet-induced obesity impairs the metabolism of pulmonary CD8+ T cells resulting in reduced effector CD8+ T cells and cytokine production following primary influenza infection.

scholarly journals Variable Increased Expression of Program Death-1 and Program Death-1 Ligands on Peripheral Mononuclear Cells Is Not Impaired in Patients with Systemic Lupus Erythematosus

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Ming-Fei Liu ◽  
Chia-Tse Weng ◽  
Meng-Yu Weng
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Normal Subjects ◽  
Functional Study ◽  
Systemic Lupus ◽  
Circulating T Cells ◽  
And Function

Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression of PD-1 molecule and/or its ligands was demonstrated in human diseases including rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells and monocytes from patient with systemic lupus erythematosus (SLE). The results showed that patients with SLE had significantly increased percentages of PD-1-expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2-expressing CD14+B monocytes. In selected SLE patients and normal subjects, functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially increased the production of IL-2, IFN-γand IL-10, the amplitude of increase roughly ranged from one to three times. There were no significant differences of the enhancing effects on cytokine production by blockage of PD-1/PDL pathway between SLE patients and normal subjects. The study indicates that there are no intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC in patients with SLE.

Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3871-3880 ◽  
Author(s):  
Marion Lambert ◽  
Monique Gannagé ◽  
Alexandre Karras ◽  
Michal Abel ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Cd8 Cells ◽  
Hhv8 Infection ◽  
Latently Infected ◽  
And Function ◽  
Cellular Immune

AbstractIt is unclear how the immune response controls human herpesvirus 8 (HHV8; also known as Kaposi sarcoma–associated herpesvirus [KSHV]) replication and thereby prevents Kaposi sarcoma (KS). We compared CD8 T-cell responses to HHV8 latent (K12) and lytic (glycoprotein B, ORF6, ORF61, and ORF65) antigens in patients who spontaneously controlled the infection and in patients with posttransplantation, AIDS-related, or classical KS. We found that anti-HHV8 responses were frequent, diverse, and strongly differentiated toward an effector phenotype in patients who controlled the infection. Conversely, HHV8-specific CD8 cells were very rare in patients who progressed to KS, and were not recruited to the tumoral tissue, as visualized by in situ tetramer staining of KS biopsies. Last, HHV8-specific CD8 T cells were observed in a seronegative recipient of an HHV8infected graft who remained persistently aviremic and antibody negative, suggesting that specific cytotoxic T lymphocytes (CTLs) may provide protection from persistent HHV8 infection. These results support the crucial role of cellular immune responses in controlling HHV8 replication, in preventing malignancies in latently infected subjects, and in conferring genuine resistance to persistent infection. They may also have important implications for the design of prophylactic and therapeutic HHV8 vaccines, and for adoptive immunotherapy of KS.

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