scholarly journals Evaluation of lymphocyte subtypes in COVID-19 patients

2021 ◽  
Author(s):  
Mitra Rezaei ◽  
Majid Marjani ◽  
Payam Tabarsi ◽  
Afshin Moniri ◽  
Mihan purabdollah ◽  
...  
Keyword(s):  
T Cells ◽  
Cohort Study ◽  
Immune System ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Lymphocyte Subsets ◽  
Peripheral Lymphocyte ◽  
Absolute Count ◽  
The Mean ◽  
The Many

Background: Although the many aspects of COVID-19 have not been yet recognized, it seems that the dysregulation of the immune system has a very important role in the progression of the disease. In this study the lymphocyte subsets were evaluated in COVID-19 patients with different severity. Methods: In this prospective study, the levels of peripheral lymphocyte subsets (CD3+, CD4+, CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were measured in 67 confirmed patients with COVID-19 on the first day of admission. Results: The mean age of cases was 51.3 plus-or-minus sign 14.8 years. Thirty-two patients (47.8%) were classified as severe cases and 11 (16.4%) patients were categorized as critical. The frequency of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells; and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, CD16+56+ lymphocytes were lower in more severe cases in comparison to milder cases. Percentages of lymphocytes, T cells, and NK cells were significantly lower inthe patients who died (p= 0.002 and P= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study suggests that the frequency of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells were difference in the severe COVID-19 patients. Moreover, lower frequency of , T cells, and NK cells are predictors of mortality of these patients.

Long Lasting Alteration of Natural Killer Cells Post-Chemotherapy in Elderly Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1653-1653
Author(s):  
Daniel Olive ◽  
Nicolas Anfossi ◽  
Pascale Andre ◽  
Jerome Rey ◽  
Florence Orlanducci ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Elderly Patients ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Time Points ◽  
Early Stages ◽  
Cell Counts

Abstract Abstract 1653 Poster Board I-679 Background The immune system is involved in AML control and Natural Killer (NK) cells are among the most promising effectors. The therapeutic potential of NK cells has been revealed by the Killer Immunoglobulin Receptor (KIR) mismatch allogeneic transplant model where the anti-leukemic effect of the graft, is due to unleashed NK cells towards AML blasts, as suggested by enhanced in vitro lytic activity of KIR-HLA mismatched donor NK cells against recipient blasts (Miller et al. 2005; Ruggeri et al. 2002). Receptors involved in the function of NK cells against AML blasts have been identified (Pende et al., 2005). Some of these receptors are altered in AML patients at diagnosis and might be involved in the immune escape of AML blasts (Costello et al., 2002). However, the status of NK cells during early stages of patient's chemotherapy (CT) treatment is unknown. The present study monitored status of NK cells during early stages following patient's remission after CT that may be critical for their long lasting clinical response, and results might provide new targets for immunotherapy. Methods We enrolled 20 elderly patients (60 to 80 years old) with non promyelocytic AML in first CR following induction and pre-consolidation CT with normal renal and hepatic functions. Patient peripheral NK, gd T and CD8 T cells were analyzed before consolidation CT and every other week after treatment for 8 weeks. 6-colors flow cytometry was performed to investigate the expression of MHC receptors (CD158a, b, e, i, CD85j and NKG2A), activating receptors (NKp30, NKp46, NKG2D, CD16, DNAM-1, 2B4) as well as their differentiation status (perforin and granzyme expression). Their function, as determined by cytotoxicity (51Cr release and CD107 expression) and cytokine production (intracellular staining of IFN-g), was analyzed using purified NK cells stimulated by K562, or in redirected assays using NKp30, NKp46 and CD16 mAbs. Results NK cell counts were depressed away from the induction and pre-consolidation CT as compared to NK cell counts of age-matched controls (ctl) (95±107 NK/μL vs 229±91 NK/μL respectively); they were further depressed during the first 2 weeks post-consolidation CT (55±57 NK/μL), but were back to pre-consolidation CT level at 4 weeks (105±102 NK/μL). In contrast, CD8 T cells and gd T cells counts were normal even at early times post-CT. Expression of 2B4 was depressed at all time points. In contrast, NKp30 expression was lower at diagnosis and close to ctl level post-consolidation CT (p=0.0003) and NKp46 expression increased after CT (p<0.0001). Sizes of NK cell subsets expressing CD158a or CD158b in patients post-induction and consolidation CT were smaller than those of ctl (% CD158a+: p=0.003; % CD158b+: p=0.014). In contrast the NKG2A or CD85j positive NK cell subsets were either unchanged or slightly increased respectively at all time points (p=0.0015 for CD85j+). Moreover, sizes of perforin or granzyme positive NK cell subsets were increased in treated AML patients (% Granzyme+: p= 0.0125 and % Perforin+: p=0.0268). In addition, we observed an important heterogeneity in the expression of the surface receptors among patients that is currently analyzed with respect to the duration of the CR. Finally, NK cell cytoxicity was comparable at all time points to the one of age-matched ctl. In contrast, IFN-g secretion was decreased, at all time points, against K562 or in redirected assays using CD16 mAb and almost abolished using redirected assay with NKp30 mAb. Conclusions This study demonstrates that in elderly AML patients in CR after CT (1) several alterations are detected at all time points, (2) NK cell number is lower and (3) IFN-g secretion is impaired. However NK cytotoxic function is comparable to age-matched controls. The likely basis of the complex pattern of modifications might rely on an interplay between the direct and indirect effects of chemotherapy, activation of immune system, NK cell differentiation and its interaction with AML blasts. Altogether this study indicates that new immunotherapeutic approaches might be used to increase NK cell numbers and functions (cytotoxicity and IFN-g secretion) at early times post-CT in elderly patients with AML. Disclosures Romagne: Innate Pharma: Employment.

scholarly journals Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

2020 ◽  
Author(s):  
Hasi Chaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Circulating Cytokines

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

CAR-Engineered T Cells Specific for the Elotuzumab Target SLAMF7 Eliminate Primary Myeloma Cells and Confer Selective Fratricide of SLAMF7+ Normal Lymphocyte Subsets

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 115-115 ◽  
Author(s):  
Sophia Danhof ◽  
Tea Gogishvili ◽  
Silvia Koch ◽  
Martin Schreder ◽  
Stefan Knop ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Lymphocyte Subsets ◽  
Normal Lymphocyte ◽  
Car T Cells ◽  
Car T ◽  
T Cell Lines

Abstract Background: SLAMF7 (CS1, CD319) is uniformly and highly expressed in multiple myeloma (MM) where it promotes adhesion and survival of malignant plasma cells (mPCs) in the bone marrow niche. It is absent on normal solid organ tissues but known to be expressed on lymphocyte subsets (T, B and NK cells). Clinical evaluation of the anti-SLAMF7 monoclonal antibody (mAb) Elotuzumab (huLuc63) has resulted in marked reversible lymphodepletion and conferred potent anti-MM efficacy in combination therapy. Here, we evaluated the potential to generate SLAMF7-directed chimeric antigen receptor (CAR) modified T cells from previously treated MM patients and analyzed their potency against autologous mPCs as well as fratricidal activity against normal lymphocyte subsets. Methods: Flow cytometric analyses for SLAMF7 expression on mPCs and normal lymphocyte subsets of MM patients (n=67) and healthy donors (n=20) was performed using specific mAbs and matched isotype controls. A SLAMF7-specific CAR was constructed using the VH/VL targeting domains of mAb huLuc63, fused to an Ig-Fc spacer and a signaling module of CD3ζ and CD28. Lentiviral gene transfer was performed into CD3/CD28-bead stimulated bulk CD4+ and CD8+ T cells of MM patients (n=7). CAR transgene positive T cells were enriched using an EGFRt transduction marker and expanded for functional analyses. Results: We confirmed high SLAMF7 expression levels on mPCs in all analyzed samples and detected SLAMF7 expression on a fraction of normal lymphocytes obtained from peripheral blood of MM patients, including naïve and memory CD4+ (95% CI: 33-59%) and CD8+ T cells (75-95%), B cells (25-35%) and NK cells (94-98%). Remarkably, the proportion of SLAMF7+ cells was significantly higher in MM patients compared to healthy donors in all corresponding lymphocyte subsets (p<0.05). Despite high level SLAMF7 expression on the input T cell population, functional CD4+ and CD8+ T cells expressing the SLAMF7-CAR could be readily generated in all 7 MM patients, and expanded to therapeutically relevant doses in a single expansion cycle following enrichment (>107 cells). We analyzed the kinetics of SLAMF7 expression on CD4+ and CD8+ CAR T cells during the manufacturing process and detected rapid disappearance of SLAMF7+ T cells in T cell lines modified with the SLAMF7-CAR. By contrast unmodified T cells and T cell lines expressing a CD19-CAR retained a significant proportion of SLAMF7+ T cells, suggesting that expression of the SLAMF7-CAR induced killing of SLAMF7+ T cells. In vitro functional testing of SLAMF7-CAR CD4+ and CD8+ T-cell lines confirmed potent specific lysis of SLAMF7+ MM cell lines including MM1.S and OPM-2 and stable SLAMF7-transfectants of K562, as well as antigen specific IFNγ secretion and productive proliferation. In a flow cytometry based cytotoxicity assay, co-incubation of mPCs with autologous (or allogeneic) SLAMF7-CAR T cells resulted in elimination of >90% of mPCs after a 4-hour incubation period, whereas CD19-CAR or unmodified T cells had no discernible effects. Moreover, in an in vivo xenograft MM model (NSG/MM1.S) a single administration of SLAMF7-CAR T cells resulted in complete MM clearance and long-term survival, whereas mice treated with CD19-CAR or unmodified T cells rapidly expired from progressive disease. Finally, we analyzed the fratricidal potential of SLAMF7-CAR T cells to predict hematologic toxicities that might occur in a clinical setting. Co-incubation of purified CD4+ and CD8+ primary T cells, B cells and NK cells with SLAMF7-CAR T cells resulted in rapid and specific elimination of only SLAMF7+ subsets, whereas SLAMF7- cells remained viable and functional as confirmed for CD4+ and CD8+ T cells by inducible IFNγ secretion. Conclusion: Our data demonstrate that SLAMF7-specific CAR T cells can be reproducibly generated from MM patients and exert remarkable anti-myeloma efficacy in pre-clinical models in vitro and in vivo. Lymphocytic fratricide does not preclude the manufacture of SLAMF7-CAR T cells but might be associated with acute (cytokine storm) or chronic (viral infections) side effects in a clinical setting. However, such toxicities may be prevented e.g. by preparative lymphodepletion and antiviral prophylaxis and enable the implementation of SLAMF7-CAR T cell therapy as a safe and effective modality in the treatment of MM. Disclosures Knop: Celgene Corporation: Consultancy. Einsele:Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Immunoregulatory Natural Killer Cells Suppress Autoimmunity by Down-Regulating Antigen-Specific CD8+ T Cells in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4367-4379 ◽  
Author(s):  
Margret Ehlers ◽  
Claudia Papewalis ◽  
Wiebke Stenzel ◽  
Benedikt Jacobs ◽  
Klaus L. Meyer ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Lysis Activity ◽  
Nonobese Diabetic Mice

Natural killer (NK) cells belong to the innate immune system. Besides their role in antitumor immunity, NK cells also regulate the activity of other cells of the immune system, including dendritic cells, macrophages, and T cells, and may, therefore, be involved in autoimmune processes. The aim of the present study was to clarify the role of NK cells within this context. Using two mouse models for type 1 diabetes mellitus, a new subset of NK cells with regulatory function was identified. These cells were generated from conventional NK cells by incubation with IL-18 and are characterized by the expression of the surface markers CD117 (also known as c-Kit, stem cell factor receptor) and programmed death (PD)-ligand 1. In vitro analyses demonstrated a direct lysis activity of IL-18-stimulated NK cells against activated insulin-specific CD8+ T cells in a PD-1/PD-ligand 1-dependent manner. Flow cytometry analyses revealed a large increase of splenic and lymphatic NK1.1+/c-Kit+ NK cells in nonobese diabetic mice at 8 wk of age, the time point of acceleration of adaptive cytotoxic immunity. Adoptive transfer of unstimulated and IL-18-stimulated NK cells into streptozotocin-treated mice led to a delayed diabetes development and partial disease prevention in the group treated with IL-18-stimulated NK cells. Consistent with these data, mild diabetes was associated with increased numbers of NK1.1+/c-Kit+ NK cells within the islets. Our results demonstrate a direct link between innate and adaptive immunity in autoimmunity with newly identified immunoregulatory NK cells displaying a potential role as immunosuppressors.

The NK and NKT Cell Compartment Is Suppressed in CML Patients before and after Imatinib Treatment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4667-4667
Author(s):  
Christiane I.-U. Chen ◽  
Holden Maecker ◽  
Peter P. Lee
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Imatinib Mesylate ◽  
Cd8 T Cells ◽  
Lymphocyte Subsets ◽  
Nkt Cells ◽  
Healthy Controls ◽  
Nkt Cell ◽  
Cell Counts ◽  
Before And After

Abstract In CML patients, lymphocyte subsets have been shown to be disturbed. NK cells as well as CD8+ T cells have been shown to be significantly lower in patients with relapse after BMT than without relapse (Jiang et al., 1996). After successful treatment (IFN- α and BMT/SCT), MHC-restricted CD8+ T cells as well as MHC-unrestricted cytotoxic NK and lymphokine activated killer (LAK) cells play an important role in controlling the disease (Meseri et al., 1993, de Castro et al., 2003, Molldrem et al., 2000), which can lead not only to hematological, but also cytogenetic responses. The development of imatinib mesylate, a selective inhibitor of the bcr/abl tyrosine kinase, as a first-line therapy enormously enhanced treatment options for CML patients, and has led to hematologic, and occasionally cytogenetic, responses at various stages of disease. To explore, if CML patients, who develop clinical responses with imatinib mesylate treatment, have normalization of their lymphocyte subsets with restoration of CD8+ and NK cells, we studied peripheral blood T cell, B cell, and NK cell subpopulations in patients in chronic or accelerated phase before and after treatment with imatinib mesylate. In 5 CML patients, 8-color flow cytometry was applied to investigate the lymphocyte subsets using anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD56, anti-CD25, anti-CD27, and anti-CD45RA antibodies. 5 healthy donors served as controls. There was no significant difference in CD19+ B cells or CD3+ T cells as well as its CD4+ and CD8+ subsets between CML patients and healthy controls. T regulatory cells (CD4+CD25+) were also similar in patients in comparison to the healthy controls (0.6% – 3% vs 2.3%). In contrast, CD3–CD56+ NK cells (4% vs 14%, p&lt;0.05) as well as NK T cells (CD3+CD56+ 1% vs 14%, p&lt;0.02; CD8+CD56+ 2% vs 17%, p&lt;0.03) were profoundly decreased in CML patients compared to the healthy controls prior to treatment with imatinib mesylate. Importantly, these abnormalities persisted even during treatment and following hematological responses (range 10 months – 35 months) (CD3-CD56+ 4–8%, CD3+CD56+ 0.5–5.5%, CD8+CD56+ 2.7–7%). On further analysis, these NK and NKT cells were mostly effector (CD45RA+CD27−, 50–80%) or memory (CD45RA-CD27+, 10–30%) cells. These results suggest, that CML not only disturbs the myeloid and the lymphoid compartment before treatment, but persistently impairs the MHC-unrestricted cytotoxic NK cells and NKT cells after treatment with imatinib mesylate, even in patients in hematological (and cytogenetic) remission with normal white cell counts (2.0 – 8.0/nl). Further investigations are required to better understand the mechanism of the prolonged and specific NK and NKT cell suppression in imatinib mesylate treated patients, and its impact on the course of the disease.

scholarly journals Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Hasichaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
Ifn Γ

To investigate the immune status of people who previously had COVID-19 infections, we recruited two-week postrecovery patients and analyzed circulating cytokine and lymphocyte subsets. We measured levels of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells and the serum concentrations of interleukin- (IL-) 1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most postrecovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8+ T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells (51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%), and IL-17 (97.06%). Compared to healthy controls, two-week postrecovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17. Among postrecovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells were positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, postrecovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system gradually recovers following COVID-19 infection; however, the sustained hyperinflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

scholarly journals Natural Killer Cells and Innate Interferon Gamma Participate in the Host Defense against Respiratory Vaccinia Virus Infection

2015 ◽  
Vol 90 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Georges Abboud ◽  
Vikas Tahiliani ◽  
Pritesh Desai ◽  
Kyle Varkoly ◽  
John Driver ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Respiratory Tract ◽  
Vaccinia Virus ◽  
Nk Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Innate Immune ◽  
Ifn Γ

ABSTRACTIn establishing a respiratory infection, vaccinia virus (VACV) initially replicates in airway epithelial cells before spreading to secondary sites of infection, mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. We recently reported that interferon gamma (IFN-γ) produced by CD8 T cells ultimately controls this disseminated infection, but the relative contribution of IFN-γ early in infection is unknown. Investigating the role of innate immune cells, we found that the frequency of natural killer (NK) cells in the lung increased dramatically between days 1 and 4 postinfection with VACV. Lung NK cells displayed an activated cell surface phenotype and were the primary source of IFN-γ prior to the arrival of CD8 T cells. In the presence of an intact CD8 T cell compartment, depletion of NK cells resulted in increased lung viral load at the time of peak disease severity but had no effect on eventual viral clearance, disease symptoms, or survival. In sharp contrast, RAG−/−mice devoid of T cells failed to control VACV and succumbed to infection despite a marked increase in NK cells in the lung. Supporting an innate immune role for NK cell-derived IFN-γ, we found that NK cell-depleted or IFN-γ-depleted RAG−/−mice displayed increased lung VACV titers and dissemination to ovaries and a significantly shorter mean time to death compared to untreated NK cell-competent RAG−/−controls. Together, these findings demonstrate a role for IFN-γ in aspects of both the innate and adaptive immune response to VACV and highlight the importance of NK cells in T cell-independent control of VACV in the respiratory tract.IMPORTANCEHerein, we provide the first systematic evaluation of natural killer (NK) cell function in the lung after infection with vaccinia virus, a member of thePoxviridaefamily. The respiratory tract is an important mucosal site for entry of many human pathogens, including poxviruses, but precisely how our immune system defends the lung against these invaders remains unclear. Natural killer cells are a type of cytotoxic lymphocyte and part of our innate immune system. In recent years, NK cells have received increasing levels of attention following the discovery that different tissues contain specific subsets of NK cells with distinctive phenotypes and function. They are abundant in the lung, but their role in defense against respiratory viruses is poorly understood. What this study demonstrates is that NK cells are recruited, activated, and contribute to protection of the lung during a severe respiratory infection with vaccinia virus.

scholarly journals Exosome-mediated immune regulation and its clinical application

2020 ◽  
Vol 4 (1) ◽  
pp. 36
Author(s):  
Naohiro Seo
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Clinical Application ◽  
Cd8 T Cells ◽  
Direct Interaction ◽  
Tumor Stroma ◽  
Treg Cells ◽  
Abnormal Cells ◽  
Antigen Presenting

Immune system is a precise mechanism for maintenance of homeostasis by lymphocyte-mediated elimination of extracellular and intercellular pathogens, and abnormal cells in cytokine-, chemokine-, antibody-, and cytotoxic granule-dependent manners. Extracellular vesicles, e.g. exosomes, released from multivesicular endosome in immune cells have been known to be a part of the immune system. Exosomes released by antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs) regulate natural killer (NK) cells, CD8+ T cells (Cytotoxic T lymphocytes [CTLs]), and CD4+ T cells (Th cells) including Th1, Th2, and regulatory T (Treg) cells. In the anti-tumor immune system, NK cells and CTLs are mainly involved in the elimination of tumor cells by direct interaction. Recently, we clarified that tumor-infiltrating CD8+ T cells prevent tumor invasion and metastasis by exosome-mediated destruction of tumor stroma consist of mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs). In this review article, we describe the role of exosomes in controlling immune system and its clinical application.

scholarly journals Exosome-mediated immune regulation and its clinical application

2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Naohiro Seo
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Clinical Application ◽  
Cd8 T Cells ◽  
Direct Interaction ◽  
Tumor Stroma ◽  
Treg Cells ◽  
Abnormal Cells ◽  
Antigen Presenting

Immune system is a precise mechanism for maintenance of homeostasis by lymphocyte-mediated elimination of extracellular and intercellular pathogens, and abnormal cells in cytokine-, chemokine-, antibody-, and cytotoxic granule-dependent manners. Extracellular vesicles, e.g. exosomes, released from multivesicular endosome in immune cells have been known to be a part of the immune system. Exosomes released by antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs) regulate natural killer (NK) cells, CD8+ T cells (Cytotoxic T lymphocytes [CTLs]), and CD4+ T cells (Th cells) including Th1, Th2, and regulatory T (Treg) cells. In the anti-tumor immune system, NK cells and CTLs are mainly involved in the elimination of tumor cells by direct interaction. Recently, we clarified that tumor-infiltrating CD8+ T cells prevent tumor invasion and metastasis by exosome-mediated destruction of tumor stroma consist of mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs). In this review article, we describe the role of exosomes in controlling immune system and its clinical application.

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