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

2003 ◽  
Vol 71 (7) ◽  
pp. 3920-3926 ◽  
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).

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

Blood ◽  
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.

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

Biology ◽  
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.

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

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.

scholarly journals 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

2019 ◽  
Vol 13 (1) ◽  
pp. 59-64
Author(s):  
Tommy Mlambo ◽  
Mqondisi Tshabalala ◽  
Tsitsi Bandason ◽  
Kudakwashe Mhandire ◽  
Bonface Mudenge ◽  
...  
Keyword(s):  
Immune Response ◽  
Antiretroviral Therapy ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Hiv Disease ◽  
Subtype C ◽  
Cd8 T Lymphocytes ◽  
Cd8 T Lymphocyte ◽  
Cytokine Levels

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.

scholarly journals Cytotoxic T Lymphocyte Escape Variants, Induced Mutations, and Synthetic Peptides Define a Dominant H-2Kb-Restricted Determinant in Simian Virus 40 Tumor Antigen

Virology ◽  
1995 ◽  
Vol 208 (1) ◽  
pp. 159-172 ◽  
Author(s):  
Lawrence M. Mylin ◽  
Alison M. Deckhut ◽  
Robert H. Bonneau ◽  
Timothy D. Kierstead ◽  
Mary J. Tevethia ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Tumor Antigen ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Induced Mutations

scholarly journals Quantitation of CD8+ T-Lymphocyte Responses to Multiple Epitopes from Simian Virus 40 (SV40) Large T Antigen in C57BL/6 Mice Immunized with SV40, SV40 T-Antigen-Transformed Cells, or Vaccinia Virus Recombinants Expressing Full-Length T Antigen or Epitope Minigenes

2000 ◽  
Vol 74 (15) ◽  
pp. 6922-6934 ◽  
Author(s):  
Lawrence M. Mylin ◽  
Todd D. Schell ◽  
Debra Roberts ◽  
Melanie Epler ◽  
Alina Boesteanu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Full Length ◽  
Variable Regions

ABSTRACT The cytotoxic T-lymphocyte response to wild-type simian virus 40 large tumor antigen (Tag) in C57BL/6 (H2b ) mice is directed against three H2-Db -restricted epitopes, I, II/III, and V, and oneH2-Kb -restricted epitope, IV. Epitopes I, II/III, and IV are immunodominant, while epitope V is immunorecessive. We investigated whether this hierarchical response was established in vivo or was due to differential expansion in vitro by using direct enumeration of CD8+ T lymphocytes with Tag epitope/major histocompatibility complex class I tetramers and intracellular gamma interferon staining. The results demonstrate that epitope IV-specific CD8+ T cells dominated the Tag-specific response in vivo following immunization with full-length Tag while CD8+ T cells specific for epitopes I and II/III were detected at less than one-third of this level. The immunorecessive nature of epitope V was apparent in vivo, since epitope V-specific CD8+ T cells were undetectable following immunization with full-length Tag. In contrast, high levels of epitope V-specific CD8+ T lymphocytes were recruited in vivo following immunization and boosting with a Tag variant in which epitopes I, II/III, and IV had been inactivated. In addition, analysis of the T-cell receptor β (TCRβ) repertoire of Tag epitope-specific CD8+ cells revealed that multiple TCRβ variable regions were utilized for each epitope except Tag epitope II/III, which was limited to TCRβ10 usage. These results indicate that the hierarchy of Tag epitope-specific CD8+T-cell responses is established in vivo.

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

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.

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

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
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.

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

Biology ◽  
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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