Correlation of High Interleukin 17A and Interleukin 6 Levels with High Virus Load Among Subtype C HIV-infected, Antiretroviral Therapy-naive Zimbabwean Patients: A Cross-sectional Study

Introduction: In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression. We quantified Th1/Th2/Th17 cytokines in an antiretroviral therapy naïve (ART) cohort to investigate their correlation with traditional markers of HIV disease progression; CD4+ T-lymphocytes and virus load (VL). Methods: We enrolled 247 HIV-infected ART-naïve participants into the study. CD4+ T- and CD8+ T-lymphocytes were enumerated using flow cytometry. VL was quantified using the Cavidi ExaVirTM Load assay. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were quantified using the BD Cytometric Bead Array Human Th1/Th2/Th17 cytokine assay. The Kendall’s rank correlation coefficient was used to determine the correlation between log10 transformed data for cytokine levels and CD4+ T- and CD8+ T-lymphocytes, CD4/CD8 ratio, and VL. Results: The median CD4+ T- and CD8+ T-lymphocyte counts were 458 cells/µL (IQR:405-556) and 776 cells/µL (IQR:581-1064), respectively. The median CD4/CD8 ratio was 0.6 (IQR: 0.45-0.86). The median VL was log103.3.copies/mL (IQR:2.74-3.93). Low CD4+ T-lymphocyte counts (p=0.010) and CD4/CD8 ratio (p=0.044) were significantly correlated with high VL. There was no significant correlation of cytokine levels with CD4+ T-, CD8+ T-lymphocyte counts and CD4/CD8 ratio. However, high levels of IL-17A (p=0.012) and IL-6 (p=0.034) were significantly correlated with high VL. Conclusion: Our study contributes to the little knowledge available on the role of cytokine profiles in the immune response to subtype C HIV infection.

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Identification of CD8 T-Lymphocyte Epitopes in OmpB of Rickettsia conorii

Infection and Immunity ◽

10.1128/iai.71.7.3920-3926.2003 ◽

2003 ◽

Vol 71 (7) ◽

pp. 3920-3926 ◽

Cited By ~ 22

Author(s):

Zhen Li ◽

C. Marcela Díaz-Montero ◽

Gustavo Valbuena ◽

Xue-Jie Yu ◽

Juan P. Olano ◽

...

Keyword(s):

T Lymphocytes ◽

T Lymphocyte ◽

Synthetic Peptides ◽

Simian Virus 40 ◽

Simian Virus ◽

Rickettsia Conorii ◽

Mammalian Expression ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte ◽

Ifn Γ

ABSTRACT The 1.2-kb DNA fragment of the Rickettsia conorii outer membrane protein B gene (OmpB451-846) was subcloned using site-specific PCR primers and expressed as six smaller fragments: OmpB458-652, OmpB595-744, OmpB595-654, OmpB645-692, OmpB689-744, and OmpB739-848. NCTC cells transfected with a mammalian expression vector expressing the fragments OmpB689-744 and OmpB739-848 stimulated immune anti-R. conorii CD8 T lymphocytes, suggesting the presence of CD8 T-lymphocyte-stimulating epitopes on these fragments. In order to further characterize the CD8 T-lymphocyte-stimulatory elements, CD8 T-lymphocyte epitopes on OmpB689-744 and OmpB739-848 were mapped by overlapping synthetic peptides. The ability of these synthetic peptides to stimulate immune CD8 T lymphocytes was determined by gamma interferon (IFN-γ) production and cell proliferation after incubation with simian virus 40-transformed murine vascular endothelial cells in the presence of a 20 μM solution of each synthetic peptide. Five synthetic peptides, SKGVNVDTV (OmpB708-716), ANVGSFVFN (OmpB735-743), IVSGTVGGQ (OmpB749-757), ANSTLQIGG (OmpB789-797), and IVEFVNTGP (OmpB812-820), induced secretion of IFN-γ at significantly higher levels than the controls. Three of these five peptides, SKGVNVDTV (OmpB708-716), ANSTLQIGG (OmpB789-797), and IVEFVNTGP (OmpB812-820), also stimulated the proliferation of immune CD8 T lymphocytes. Significantly higher levels of specific cytotoxic T-lymphocyte killing were observed with the same three synthetic peptides, SKGVNVDTV (OmpB708-716), ANSTLQIGG (OmpB789-797), and IVEFVNTGP (OmpB812-820).

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Purified CD4 T Lymphocyte Infusion Can Result in Graft-Versus-Leukemia Reactivity without Gvhd by Recognition of Broadly Expressed Minor Histocompatibility Antigens in HLA Class-II

Blood ◽

10.1182/blood.v120.21.4116.4116 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4116-4116

Author(s):

P. van Balen ◽

C.A.M. van Bergen ◽

I. Jedema ◽

S.A.P. van Luxemburg-Heijs ◽

J.C. Harskamp ◽

...

Keyword(s):

Immune Response ◽

T Lymphocytes ◽

T Lymphocyte ◽

Hematopoietic Cells ◽

Hla Class I ◽

Class Ii ◽

Hla Class Ii ◽

Inflammatory Conditions ◽

Cd8 T Lymphocytes ◽

Hla Dr

Abstract Abstract 4116 Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) can mediate curative Graft-versus-Leukemia (GVL) reactivity although frequently at the cost of Graft-versus-Host Disease (GVHD). We previously illustrated that donor CD8 T lymphocytes recognizing HLA class-I restricted minor histocompatibility antigens (MiHAs) that are broadly expressed on tissues of the recipient cause GVL associated with GVHD, whereas T lymphocytes recognizing MiHAs selectively expressed on hematopoietic cells, including the malignant cells, can selectively mediate GVL without GVHD. Since in contrast to HLA class-I, expression of HLA class-II molecules is predominantly restricted to hematopoietic cells, we hypothesized that infused purified donor CD4 T lymphocytes may selectively recognize and eliminate hematopoietic cells from the recipient resulting in GVL without GVHD. We treated a patient with CML in blastic phase in remission after intensive chemotherapy with T cell depleted alloSCT from his HLA-identical sibling donor after myelo-ablative conditioning. After donor engraftment, recipient hematopoiesis reoccurred within 3 months to 90% of CD8 T lymphocytes, 13% of CD4 T lymphocytes and 5% of myelopoiesis. As part of a clinical trial, the patient was treated with 106/kg positively selected purified donor derived CD4 T lymphocytes resulting within 19 weeks in conversion into full donor chimerism in all hematopoietic cell lineages in the total absence of GVHD. To characterize the nature of this hematopoiesis restricted immune response, in vivo activated HLA-DR positive CD4 and CD8 T lymphocytes were clonally isolated by flowcytometric cell sorting at the time of the clinical response, expanded and tested for alloreactivity on patient and donor derived hematopoietic target cells using IFNγ ELISA. From the 204 expanding CD4 T lymphocyte clones 31 clones were alloreactive, whereas none of the 66 expanding CD8 T lymphocyte clones showed alloreactivity. To further identify the fine specificity of this hematopoiesis directed HLA class-II restricted immune response, target molecules of several T lymphocyte clones were molecularly characterized using whole genome association scanning. We first performed blocking studies with HLA class-II restricted monoclonal antibodies and identified HLA-DR to be the restriction molecule. Next, a large panel of third party EBV-LCLs was retrovirally transduced with each of the possible restriction molecules being HLA-DRB1*11:01, HLA-DRB1*15:01, HLA-DRB3*02:02 and HLA-DRB5*01:01. By comparing the recognition pattern of the transduced EBV-LCLs with the 1.1 million single nucleotide polymorphisms in each EBV-LCL, we identified 3 novel MiHAs. Synthesis and analysis of the patient and donor derived allelic peptide variants further confirmed the specificity of the MiHAs as LB-KHNYN-1K in the context of HLA-DRB5*01:01, LB-CTSB-1G in HLA-DRB1*11:01 and LB-ZDHHC13-1K in HLA-DRB1*15:01. Gene expression profiles of KHNYN (located on chromosome 14), CTSB (chromosome 8) and ZDHHC13 (chromosome 11) illustrated that the genes encoding these MiHAs were not only transcribed in hematopoietic cells, but also in other tissues including GVHD target tissues. These results further illustrated that the hematopoietic specificity of the CD4 T lymphocyte response was mainly defined by the restricted expression of the HLA-DR molecules on hematopoietic cells. We conclude that purified CD4 DLI can lead to GVL without GVHD by a selective HLA class-II restricted immune response against patient hematopoiesis. By molecular characterization of 3 novel HLA-DR restricted MiHAs we illustrated that the relative specificity of HLA class-II molecules on hematopoietic cells under non inflammatory conditions was probably responsible for this effect. Since HLA class-II is predominantly expressed on hematopoietic cells only, infusion of donor CD4 T lymphocytes under non inflammatory conditions after HLA identical alloSCT can result in efficient induction of GVL without the toxicity of GVHD. Disclosures: No relevant conflicts of interest to declare.

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IL-6, NLR, and SII Markers and Their Relation with Alterations in CD8+ T-Lymphocyte Subpopulations in Patients Treated for Lung Adenocarcinoma

Biology ◽

10.3390/biology9110376 ◽

2020 ◽

Vol 9 (11) ◽

pp. 376

Author(s):

Lorenzo Islas-Vazquez ◽

Dolores Aguilar-Cazares ◽

Miriam Galicia-Velasco ◽

Uriel Rumbo-Nava ◽

Manuel Meneses-Flores ◽

...

Keyword(s):

T Lymphocytes ◽

Lung Adenocarcinoma ◽

T Lymphocyte ◽

Median Overall Survival ◽

Neutrophil Lymphocyte Ratio ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte ◽

Adenocarcinoma Cells ◽

Chemotherapy Patients ◽

Lymphocyte Populations

Cytokines, key contributors to tumorigenesis, are mediators between inflammatory immune or nonimmune and cancer cells. Here, IL-6 production by tumor cells was assessed in a cohort of patients with lung adenocarcinoma treated with conventional therapy. IL-6 levels and neutrophil–lymphocyte ratio (NLR) or systemic immune-inflammation index (SII) markers were evaluated. Changes in pro- and anti-inflammatory cytokines, HMGB1 concentration, and CD4+ and CD8+ T-lymphocyte populations and their subpopulations were investigated. IL-6 expression was detected immunohistochemically in lung adenocarcinoma biopsies. Cytokines were quantified using the cytometric bead array, and TGF-β and HMGB-1 through ELISA. Clinical parameters were collected to assess NLR and SII. CD4+ and CD8+ T-lymphocytes and naïve, memory, and effector subpopulations were quantified by flow cytometry. The data obtained were associated with patients’ median overall survival (OS). IL-6 showed the highest increase, probably because the lung adenocarcinoma cells produced IL-6. Patients with higher OS had lower NLR and SII from the third cycle of chemotherapy. Patients with lower OS had significantly lower percentages of CD8+ T-lymphocyte and its effector subpopulations, with a concomitant increase in the naïve subpopulation. This study suggests that in addition to the known inflammatory markers, IL-6, CD8+ T-lymphocytes and their effector and naïve subpopulations could be useful as predictive markers in lung adenocarcinoma.

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Case Report: CD8+ T-Lymphocyte Deficit: A Prerequisite for Pasteurella spp. Infection?

Frontiers in Medicine ◽

10.3389/fmed.2021.668976 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eric Denes ◽

Fabrice Fiorenza ◽

Mateo Armendariz ◽

Christian Martin

Keyword(s):

Case Report ◽

T Lymphocytes ◽

Animal Models ◽

T Lymphocyte ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Cd8 T Lymphocytes ◽

Prosthetic Joint ◽

Cd8 T Lymphocyte

Background: Immunity against Pasteurella spp. is not well-known for humans.Methods: We've tested T CD8+ lymphocytes in a patient with a chronic prosthetic joint infection due to Pasteurella spp. to search for a deficit which could have favored her infection. As this deficit was found, we've searched for such a deficit in other patients with Pasteurella spp. Infections, either acute or subacute.Results: Eight patients were tested and all had a persistent T CD8+ lymphocytes deficit. This is striking as these cells are involved in the response to this type of infection in animal models.Conclusion: The authors suggest that a deficit in CD8+ T lymphocytes can be one of the causes for the onset of infections with P. multocida.

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High Frequencies of Increased Interferon-γ-Producing and/or Skewed CD8+ T Lymphocyte Subfamilies in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Blood ◽

10.1182/blood.v108.11.980.980 ◽

2006 ◽

Vol 108 (11) ◽

pp. 980-980

Author(s):

Akiko Shichishima ◽

Hideyoshi Noji ◽

Kazuhiko Ikeda ◽

Yukio Maruyama ◽

Tsutomu Shichishima

Keyword(s):

T Lymphocytes ◽

T Lymphocyte ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Interferon Γ ◽

Healthy Individuals ◽

High Frequencies ◽

Over Expression ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte ◽

Ifn Γ

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematological disorder affecting all hematopoietic lineages, which lack glycosylphosphatidylinositol (GPI)-anchored membrane proteins due to somatic mutations in the phosphatidylinositol glycan-class A gene, and is one disorder of bone marrow failure (BMF) syndromes. Autoreactive T lymphocytes are implicated in some of the immune mechanisms involved in PNH. In fact, we reported recently that the HLA-DRB1*1501 allele and HLA-A*0206 allele is frequent and is related to grading of hemolysis, respectively, in PNH patients (Shichishima T et al, Blood, 2002 and Haematologica, 2006, respectively). However, some characteristics of CD4+ and CD8+ T lymphocytes, including GPI-negative CD4+ and CD8+ T lymphocytes, in PNH patients remain unknown. To know some characteristics of CD4+ and CD8+ T lymphocytes with and without expressions of GPI proteins in PNH, we examined preferential variable beta chain (Vβ) repertoires of the T-cell receptor (TCR) and expressions of interferon-γ (IFN-γ) by flow cytometry and the TCR Vβ complementarity-determining region 3 (CDR3) spectratypes by genetic methods at the same time in CD4+CD59+, CD4+CD59−, CD8+CD59+, and/or CD8+CD59− T lymphocytes from 10 Japanese patients, including 6 and 4 with the HLA-DRB1*1501 allele and HLA-A*0206 allele, respectively, and from 5 age-matched healthy individuals. In the analyses of TCR Vβ repertoires, over-expressed TCR Vβ subfamilies were found in any T lymphocytes subsets from all the patients. We found significantly higher numbers (mean ± standard deviation; 1.9 ± 1.2) of over-expressed TCR Vβ subfamilies in CD8+CD59+ T lymphocytes from PNH patients compared with those (0 ± 0, p <0.01) from healthy individuals. In the TCR Vβ CDR3 spectratyping, skewed TCR Vβ CDR3 spectatypes were found in more than one TCR Vβ subfamilies of CD3+CD4+CD59−, CD3+CD8+CD59+, and CD3+CD8+CD59− T lymphocytes from all the PNH patients. The numbers of skewed TCR Vβ CDR3 spectatypes in CD3+CD8+CD59+ (4.0 ± 3.3) and CD3+CD8+CD59− (7.5 ± 3.9) T lymphocytes from one PNH patient were significantly greater than those in CD3+CD4+CD59+ T lymphocytes (0.6 ± 1.0, p <0.005) and CD3+CD4+CD59− (2.5 ± 1.5, p <0.002), respectively. Skewed TCR Vβ CDR3 spectatypes were found commonly in Vβ 25 subfamily of CD3+CD8+CD59+ and CD3+CD8+CD59− T lymphocytes from all of 4 PNH patients with the HLA-A*0206 allele. In the analyses of IFN-γ expressions, more than one TCR Vβ subfamiliy with over-expression of IFN-γ was found in CD8+CD59+ and/or CD8+CD59− T lymphocytes from 9 patients and in CD4+CD59+ and/or CD4+CD59− T lymphocytes from 8 patients. The numbers of TCR Vβ subfamiliy with over-expression of IFN-γ in CD8+CD59+ T lymphocytes (5.2 ± 4.3), but not in the other T lymphocyte subsets, from one PNH patient were significantly greater than those from healthy individuals (0 ± 0, p <0.05). However, there were no specific Vβ subfamilies determined by any analyses, described above, in PNH. In conclusion, we found high frequencies of increased IFN-γ-producing and/or skewed CD8+ T lymphocyte subfamilies with and/or without CD59 expression in PNH patients, suggesting that these cells may contribute to the occurrence of BMF rather than negative selection of PNH clones through action of IFN-γ in PNH.

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Identification of CD8+ T Cell-Related Genes: Correlations with Immune Phenotypes and Outcomes of Liver Cancer

Journal of Immunology Research ◽

10.1155/2021/9960905 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Qi Pan ◽

Ying Cheng ◽

Donghua Cheng

Keyword(s):

T Lymphocytes ◽

Liver Cancer ◽

T Lymphocyte ◽

Biological Processes ◽

Single Cell Sequencing ◽

Cd8 T Lymphocytes ◽

Tumor Purity ◽

Cd8 T Lymphocyte ◽

Coexpression Module ◽

Coexpressed Genes

Purpose. Treatment outcomes for advanced liver cancer are poor. Immunotherapy is a treatment strategy that has been widely used to treat other cancers. Studies have shown that CD8+ T lymphocytes are essential factors affecting the efficacy of immunotherapy. We used computational biology methods to determine the coexpressed gene network that promotes CD8+ T lymphocyte infiltration. Method. We obtained the liver cancer gene matrix and clinical follow-up information data from TCGA liver hepatocellular carcinoma FPKM. We obtained single nucleotide polymorphism (SNP) data to evaluate the tumor mutation burden. The “estimate” package and the CIBERSORT algorithm were used to evaluate tumor purity and the proportion of CD8+ T lymphocytes in the liver cancer cohort. We used the gene expression matrix of liver cancer and the relative proportion of CD8+ T lymphocytes as input files and performed WGCNA based on this analysis. The weighted coexpression network identified the most CD8+ T lymphocyte-related coexpression modules in liver cancer. Then, we analyzed the biological processes involved in the module. We determined the coexpression module with CD8+ T lymphocyte infiltration in terms of data and function. We then screened the factors in the coexpression module correlated with CD8+ T lymphocyte content greater than 0.4. Finally, the expression levels of these factors were verified at the protein level using immunohistochemistry and single-cell sequencing. Results. We determined the CD8+ T lymphocyte proportions that correlated with coexpression networks. Four coexpressed genes (C1QC, CD3D, GZMA, and PSMB9) were identified as CD8+ T cell coexpression genes that promoted infiltration of CD8+ T cells. Because the factors in the coexpression network often participate in similar biological processes, we found that these factors were most related to antigen processing and presentation of peptide antigen through functional enrichment. In the clinical phenotype analysis, we found that 18 factors can be used as independent prognostic protective factors. We found that these factors were significantly negatively correlated with tumor purity and negatively correlated with M2 macrophages in the immunophenotyping analysis. Using immunohistochemistry and single-cell sequencing analysis, we found that CD3D antibody staining was weaker in tumor tissues than normal tissues and was related to CD8+ T cells. Conclusion. These coexpressed genes were positively related to the high infiltration proportion of CD8+ T lymphocytes in an antigen presentation process. The biological process might provide new directions for patients who are insensitive to immune therapy.

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Changes in T Lymphocyte Subsets in Different Tumors Before and After Radiotherapy: A Meta-analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.648652 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qin Wang ◽

Shangbiao Li ◽

Simiao Qiao ◽

Zhihao Zheng ◽

Xiaotong Duan ◽

...

Keyword(s):

Immune Response ◽

T Lymphocytes ◽

T Lymphocyte ◽

Peripheral Blood ◽

Lymphocyte Subsets ◽

Meta Analysis ◽

Tumor Patients ◽

T Lymphocyte Subsets ◽

Cd8 T Lymphocytes ◽

Before And After

PurposeRadiation therapy (RT) induces an immune response, but the relationship of this response with tumor type is not fully understood. This meta-analysis further elucidated this relationship by analyzing the changes in T lymphocyte subsets in different tumors before and after radiotherapy.MethodsWe searched English-language electronic databases including PubMed, EMBASE, and the Cochrane Library to collect studies on the changes in peripheral blood CD3+ T lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes before and after radiotherapy in tumor patients from January 2015 to April 2021. The quality of the included literature was evaluated using the NOS scale provided by the Cochrane Collaboration, and statistical software RevMan 5.4 was used to analyze the included literature. P<0.05 was considered to indicate statistical significance.ResultsA total of 19 studies in 16 articles involving 877 tumor patients were included. All data were collected within 1 month before or after radiotherapy. Meta-analysis showed that numbers of CD3+ T lymphocytes (SMD: -0.40; 95% CI [-0.75, -0.04]; p = 0.03) and CD4+ T lymphocytes (SMD: -0.43; 95% CI: [-0.85, -0.02]; p = 0.04) were significantly reduced after radiotherapy compared with before treatment, but there was no statistically significant difference for CD8+ T lymphocytes (SMD: 0.33; 95% CI: [-0.88, 0.74]; p = 0.12). Subgroup analysis showed that peripheral blood T lymphocytes decreased in head and neck cancer. However, in prostate cancer and breast cancer, there was no significant change in peripheral blood. 1 month after radiotherapy, it has a potential proliferation and activation effect on lymphocytes in esophageal cancer and lung cancer. The results showed that CD8+T lymphocytes increased in peripheral blood after SBRT. Radiotherapy alone reduced CD3+ T lymphocyte numbers.ConclusionsWithin 1 month of radiotherapy, patients have obvious immunological changes, which can cause apoptosis and reduction of T lymphocytes, and affect the balance of peripheral blood immune cells. The degree of immune response induced by radiotherapy differed between tumor types.

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Level of CD8 T Lymphocytes Activation in HIV-Infected Pregnant Women: In the Context of CD38 and HLA-DR Activation Markers

Interdisciplinary Perspectives on Infectious Diseases ◽

10.1155/2014/715279 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Stanslaus Musyoki ◽

Simeon Mining ◽

Paul Nyongesa

Keyword(s):

T Lymphocytes ◽

Pregnant Women ◽

T Lymphocyte ◽

Immune Activation ◽

Hiv Positive ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte ◽

Hla Dr ◽

Study Results ◽

Study Participants

Background. To date the effect of pregnancy on the immune activation of CD8 T cells that may affect HIV disease progression has not been well studied and remains unclear.Objective.To determine the effect of pregnancy on CD8 T lymphocyte activation and its relationship with CD4 count in HIV infected pregnant women.Study Design. Case control.Study Site. AMPATH and MTRH in Eldoret, Kenya.Study Subjects. Newly diagnosed asymptomatic HIV positive pregnant and nonpregnant women with no prior receipt of antiretroviral medications.Study Methods. Blood samples were collected from the study participants and levels of activated CD8 T lymphocytes (CD38 and HLA-DR) were determined using flow cytometer and correlated with CD4 counts of the study participants. The descriptive data focusing on frequencies, correlation, and cross-tabulations was statistically determined. Significance of the results was set atP<0.05.Results. HIV positive pregnant women had lower activated CD8 T lymphocyte counts than nonpregnant HIV positive women. Activated CD8 T lymphocyte counts were also noted to decrease in the second and third trimesters of pregnancy.Conclusion. Pregnancy has a significant suppression on CD8+ T lymphocyte immune activation during HIV infections. Follow-up studies with more control arms could confirm the present study results.

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Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes’ iTNF-α Expression

Biology ◽

10.3390/biology10080735 ◽

2021 ◽

Vol 10 (8) ◽

pp. 735

Author(s):

Gabriele Madonna ◽

Silvia Sale ◽

Mariaelena Capone ◽

Chiara De Falco ◽

Valentina Santocchio ◽

...

Keyword(s):

T Lymphocytes ◽

T Lymphocyte ◽

Inflammatory Cells ◽

Retrospective Assessment ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte ◽

Tnf Α ◽

Cellular Mediators ◽

Novel Coronavirus

In December 2019, a novel coronavirus, “SARS-CoV-2”, was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

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Incomplete Cd8+ T Lymphocyte Differentiation as a Mechanism for Subdominant Cytotoxic T Lymphocyte Responses to a Viral Antigen

Journal of Experimental Medicine ◽

10.1084/jem.191.10.1687 ◽

2000 ◽

Vol 191 (10) ◽

pp. 1687-1698 ◽

Cited By ~ 52

Author(s):

Juliet V. Spencer ◽

Thomas J. Braciale

Keyword(s):

T Lymphocytes ◽

T Lymphocyte ◽

Large Population ◽

Cytolytic Activity ◽

Class I ◽

Activation Markers ◽

Lymphocyte Differentiation ◽

Ctl Response ◽

Cd8 T Lymphocytes ◽

Cd8 T Lymphocyte

CD8+ cytotoxic T lymphocytes (CTLs) recognize antigen in the context of major histocompatibility complex (MHC) class I molecules. Class I epitopes have been classified as dominant or subdominant depending on the magnitude of the CTL response to the epitope. In this report, we have examined the in vitro memory CTL response of H-2d haplotype murine CD8+ T lymphocytes specific for a dominant and subdominant epitope of influenza hemagglutinin using activation marker expression and staining with soluble tetrameric MHC–peptide complexes. Immune CD8+ T lymphocytes specific for the dominant HA204-210 epitope give rise to CTL effectors that display activation markers, stain with the HA204 tetramer, and exhibit effector functions (i.e., cytolytic activity and cytokine synthesis). In contrast, stimulation of memory CD8+ T lymphocytes directed to the subdominant HA210-219 epitope results in the generation of a large population of activated CD8+ T cells that exhibit weak cytolytic activity and fail to stain with the HA210 tetramer. After additional rounds of restimulation with antigen, the HA210-219–specific subdominant CD8+ T lymphocytes give rise to daughter cells that acquire antigen-specific CTL effector activity and transition from a HA210 tetramer–negative to a tetramer-positive phenotype. These results suggest a novel mechanism to account for weak CD8+ CTL responses to subdominant epitopes at the level of CD8+ T lymphocyte differentiation into effector CTL. The implications of these findings for CD8+ T lymphocyte activation are discussed.

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