scholarly journals Atypical lymphoid cells circulating in blood in COVID-19 infection: morphology, immunophenotype and prognosis value

2020 ◽  
pp. jclinpath-2020-207087
Author(s):  
Anna Merino ◽  
Alexandru Vlagea ◽  
Angel Molina ◽  
Natalia Egri ◽  
Javier Laguna ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Automatic System ◽  
Lymphoid Cells ◽  
Effector Memory ◽  
Laboratory Findings ◽  
Deep Blue ◽  
Sensitivity Specificity ◽  
Reactive Lymphocytes ◽  
D Dimer

AimsAtypical lymphocytes circulating in blood have been reported in COVID-19 patients. This study aims to (1) analyse if patients with reactive lymphocytes (COVID-19 RL) show clinical or biological characteristics related to outcome; (2) develop an automatic system to recognise them in an objective way and (3) study their immunophenotype.MethodsClinical and laboratory findings in 36 COVID-19 patients were compared between those showing COVID-19 RL in blood (18) and those without (18). Blood samples were analysed in Advia2120i and stained with May Grünwald-Giemsa. Digital images were acquired in CellaVisionDM96. Convolutional neural networks (CNNs) were used to accurately recognise COVID-19 RL. Immunophenotypic study was performed throughflow cytometry.ResultsNeutrophils, D-dimer, procalcitonin, glomerular filtration rate and total protein values were higher in patients without COVID-19 RL (p<0.05) and four of these patients died. Haemoglobin and lymphocyte counts were higher (p<0.02) and no patients died in the group showing COVID-19 RL. COVID-19 RL showed a distinct deep blue cytoplasm with nucleus mostly in eccentric position. Through two sequential CNNs, they were automatically distinguished from normal lymphocytes and classical RL with sensitivity, specificity and overall accuracy values of 90.5%, 99.4% and 98.7%, respectively. Immunophenotypic analysis revealed COVID-19 RL are mostly activated effector memory CD4 and CD8 T cells.ConclusionWe found that COVID-19 RL are related to a better evolution and prognosis. They can be detected by morphology in the smear review, being the computerised approach proposed useful to enhance a more objective recognition. Their presence suggests an abundant production of virus-specific T cells, thus explaining the better outcome of patients showing these cells circulating in blood.

scholarly journals Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis

2019 ◽  
Vol 5 (3) ◽  
pp. 63
Author(s):  
Alice Bayiyana ◽  
Samuel Okurut ◽  
Rose Nabatanzi ◽  
Godfrey Zziwa ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Cryptococcal Meningitis ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Subset

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.

Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys

2010 ◽  
Vol 23 (4) ◽  
pp. 194-203 ◽  
Author(s):  
Kiyoshi Setoguchi ◽  
Hidehiro Kishimoto ◽  
Sakiko Kobayashi ◽  
Hiroaki Shimmura ◽  
Hideki Ishida ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Potential Role ◽  
Mixed Chimerism ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cynomolgus Monkeys

IL-8 responsiveness defines a subset of CD8 T cells poised to kill

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3463-3471 ◽  
Author(s):  
Christoph Hess ◽  
Terry K. Means ◽  
Patrick Autissier ◽  
Tonia Woodberry ◽  
Marcus Altfeld ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Immune System Activation ◽  
Hiv 1

CD8 T cells play a key role in host defense against intracellular pathogens. Efficient migration of these cells into sites of infection is therefore intimately linked to their effector function. The molecular mechanisms that control CD8 T-cell trafficking into sites of infection and inflammation are not well understood, but the chemokine/chemokine receptor system is thought to orchestrate this process. Here we systematically examined the chemokine receptor profile expressed on human CD8 T cells. Surprisingly, we found that CXC chemokine receptor 1 (CXCR1), the predominant neutrophil chemokine receptor, defined a novel interleukin-8/CXC ligand 8 (IL-8/CXCL8)–responsive CD8 T-cell subset that was enriched in perforin, granzyme B, and interferon-γ (IFNγ), and had high cytotoxic potential. CXCR1 expression was down-regulated by antigen stimulation both in vitro and in vivo, suggesting antigen-dependent shaping of the migratory characteristics of CD8 T cells. On virus-specific CD8 T cells from persons with a history of Epstein-Barr virus (EBV) and influenza infection, CXCR1 expression was restricted to terminally differentiated effector memory cells. In HIV-1 infection, CXCR1-expressing HIV-1–specific CD8 T cells were present only in persons who were able to control HIV-1 replication during structured treatment interruptions. Thus, CXCR1 identifies a subset of CD8 T cells poised for immediate cytotoxicity and early recruitment into sites of innate immune system activation.

scholarly journals AB0041 CD8+ T CELLS HAVE AN ELEVATED PROLIFERATIVE CAPACITY IN GIANT CELL ARTERITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1323.1-1323
Author(s):  
R. Reitsema ◽  
R. Hid Cadena ◽  
W. Abdulahad ◽  
A. Boots ◽  
P. Heeringa ◽  
...  
Keyword(s):  
T Cells ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Newly Diagnosed ◽  
Proliferative Capacity ◽  
Ki 67 ◽  
Age And Sex

Background:Giant cell arteritis (GCA) is the most frequent form of systemic vasculitis affecting the large- and medium-sized vessels. The involvement of innate immune cells and CD4+ T cells in the pathogenesis of GCA has been extensively studied. Interestingly, recent findings suggest a role for CD8+ T cells in disease development (1). However, CD8+ subsets and their functional capacities have not yet been studied in detail.Objectives:This study aims to characterize the phenotype and proliferative capacity of CD8+ T cells in newly diagnosed GCA patients and GCA patients in remission compared to healthy age- and sex- matched controls.Methods:To determine the phenotype of CD8+ T cells in GCA, newly diagnosed, untreated GCA patients (baseline, n=14), GCA patients in stable glucocorticoid-free remission (GC-FR, n=10) and age- and sex-matched healthy controls (HCs, n=18) were enrolled. Peripheral blood mononuclear cells (PBMCs) were stained with fluorochrome-conjugated antibodies directed against CD3, CD4, CD8, CCR7, CD45RO, Ki-67, CD69 and CD25 and analyzed by flow cytometry. The following differentiation subsets were defined: CD8+ T naive (CD45RO-CCR7+), central memory (TCM, CD45RO+CCR7+), effector memory (TEM, CD45RO+CCR7-) and effector memory re-expressing CD45RA (TEMRA, CD45RO-CCR7-) cells. Secondly, the proliferative capacity of CD8+ T cells was determined in isolated CD3+ T cells of 10 GCA baseline, 10 GCA GC-FR patients and 19 HCs after 5 days of stimulation with plate-bound anti-CD3 or anti-CD3 plus soluble anti-CD28 using a dye-based proliferation assay.Results:A reduced frequency of CD8+ TEMcells was found in GCA baseline patients compared to HCs (p=0.025). Furthermore, a higher frequency of Ki-67+ cells was detected among CD8+ TEMcells in GCA baseline patients than in HCs (p=0.0007), suggesting a higher proliferative activityin vivo.In addition,in vitrostimulation with anti-CD3 and anti-CD3+anti-CD28 led to higher percentages of divided CD8+ T cells in GCA baseline and GC-FR patients than in HCs (p<0.05). Moreover, the frequencies of CD8+ TEMRAcells and the percentage of divided CD8+ T cells upon CD3 stimulation strongly correlated in GCA baseline patients (R=0.79, p=0.009) and GCA GC-FR patients (R=0.67, p=0.039) but not in HCs (R=0.31, p=0.25).Conclusion:GCA baseline patients demonstrate a higher frequency of proliferating circulating CD8+ TEMcells, defined by Ki-67 expression, than HCs. In addition, functional data on induced proliferative capacity suggest that CD8+ T cells from GCA baseline patients are more rapidly activated by crosslinking CD3 and CD3+CD28, suggesting either reduced regulation in these patients or more intrinsic threshold changes. Furthermore, the induced proliferative capacity is also elevated in patients in stable glucocorticoid-free remission. Whether the increased proliferative capacity of total CD8+ T cells in GCA patients is causally linked to the increased frequencies of CD8+ TEMRAcells in these patients requires further investigation.References:[1]Samson M, Ly KH, Tournier B, Janikashvili N, Trad M, Ciudad M, et al. Involvement and prognosis value of CD8+ T cells in giant cell arteritis. J Autoimmun. 2016;72:73–83.Disclosure of Interests:Rosanne Reitsema: None declared, Rebeca Hid Cadena: None declared, Wayel Abdulahad: None declared, Annemieke Boots Consultant of: Grünenthal Gmbh until 2017, Peter Heeringa: None declared, Elisabeth Brouwer Consultant of: Roche (consultancy fee 2017 and 2018 paid to the UMCG), Speakers bureau: Roche (2017 and 2018 paid to the UMCG)

scholarly journals CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

2004 ◽  
Vol 200 (11) ◽  
pp. 1407-1417 ◽  
Author(s):  
Adrian F. Ochsenbein ◽  
Stanley R. Riddell ◽  
Michele Brown ◽  
Lawrence Corey ◽  
Gabriela M. Baerlocher ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Effector Memory ◽  
Term Survival ◽  
Functional Consequences

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response.

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