scholarly journals Humoral and cellular indices of immunity in newborns with early realization of the allergically changed reactivity

2021 ◽  
Vol 82 (1) ◽  
pp. 22-24
Author(s):  
A. G. Shamova ◽  
E. V. Agafonova ◽  
A. N. Stepanova ◽  
T. G. Malanicheva
Keyword(s):  
Immune Status ◽  
Neonatal Period ◽  
Cell Phenotype ◽  
Response Type ◽  
Immunocompetent Cell ◽  
Activation Markers ◽  
Perinatal Development ◽  
Early Change ◽  
Immunologic Reactivity

The complex immunologic examination in 39 children aged 2 to 28 days with early realization of the allergically changed reactivity in boys 61,5%, in girls 38,5% is performed. The peculiarities of immunologic reactivity in children with early realization of the allergically changed reactivity (the increase of the immune regulatory index due to the deficiency of CD 8+ lymphocytes, the increased expression of activation markers, the increase of Ig E) show the prevalence of the atopic response type. Uniformity of changes of the immune status indices in early and late neonatal period testifies the intrauterine and/or early change of immunocompetent cell phenotype under the influence of perinatal development factors of a child

Abstract W P87: Characteristics of T-cells Infiltrating Ruptured Intracranial Aneurysm

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Roger M Krzyzewski ◽  
Magdalena K Stachura ◽  
Mariusz Krupa ◽  
Rafal Morga ◽  
Agnieszka Sagan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Intracranial Aneurysm ◽  
Peripheral Blood ◽  
Histological Finding ◽  
Cell Phenotype ◽  
Double Negative ◽  
Activation Markers ◽  
Hla Dr ◽  
Ruptured Intracranial Aneurysm

Introduction: Recently the role of adaptive immunity has been implied by microarray studies. But the results are contradictory. T-cell infiltration is a frequent histological finding in ruptured IA, T-cell phenotype, characteristic and true quantitation remains unknown. We preformed a prospective study to determine the subpopulation and expression of activation markers of T-cells infiltrating ruptured IA in relation to peripheral blood. Hypothesis: IA have different subsets and activation levels of T-cells than peripheral blood. Methods: We collected the tissue of ruptured IA of 8 patients operated on within 24 hours after subarachnoid hemorrhage symptoms onset. IA tissue was digested, stained with fluorescently labeled monoclonal antibodies and submitted to flow cytometry. In addition we collected and analyzed venous blood from 6 age, sex and risk factor-matched controls. Results: CD4+ cells are less prevalent in IA tissue than in peripheral blood (42.14±17.28 vs. 65.88±5.32%; p=0.011), while there was no difference in CD8+ T-cells infiltrating IA (30.28±9.07 vs. 27.78±5.45%; p=0.585), and double negative (CD4-CD8-CD3+) T-cells were more prevalent in wall of IA than in circulation, (15.68±11.94 vs. 2.81±1.32%; p=0.026). Importantly, CD4+ infiltrating IA wall showed higher expression of HLA-DR (25.9±6.42 vs. 9.19± 3.58%; p<0.001) higher expression of CD 69 (26.8±19.66 vs. 2.73±0.93%; p=0.014). Similarly, there significantly more CD8+ cells showed HLA-DR+ in the IA than in blood. (45.96±15.57 vs. 22.47±11.46%; p=0.018) and CD69 (30.32±22.73 vs. 5.03±1.55%; p=0.022). Double negative cells in IA also had higher expression of HLA-DR (46.56±21.40 vs. 22.58±5.1%; p=0.025), CD69 (31.05±16.79 vs. 7.83±2.05%; p=0.016). Conclusion: The tissue of ruptured IA is highly infiltrated by T-cells which show high expression of activation markers such as CD69 or HLA-DR. The importance of these cells to immunopathogenesis of intracranial aneurysm rupture should be further characterized.

scholarly journals Autologous culture model of nodal B-cell lymphoma identifies ex vivo determinants of response to bispecific antibodies

2021 ◽  
Author(s):  
Tobias Roider ◽  
Berit J. Brinkmann ◽  
Vladislav Kim ◽  
Mareike Knoll ◽  
Carolin Kolb ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Ex Vivo ◽  
B Cell Lymphoma ◽  
Bispecific Antibodies ◽  
Cell Phenotype ◽  
Activation Markers ◽  
Culture Model

Bispecific antibodies (BsAb) can induce long-term responses in refractory and relapsed B cell lymphoma patients. Nevertheless, response rates across patients are heterogenous and the factors determining quality and duration of responses are poorly understood. In order to identify key determinants of response to BsAb, we established a primary, autologous culture model allowing us to mimic treatment with CD3xCD19 and CD3xCD20 BsAb within the lymph node microenvironment ex vivo. T cell-mediated killing of lymphoma cells and proliferation of T cells varied significantly among patients but highly correlated between BsAb targeting CD20 or CD19. Ex vivo response to BsAb was significantly associated with expansion of T cells and secretion of effector molecules, such as granzyme B and perforin, but not with expression of T cell exhaustion (e.g. PD1, TIM3) or activation markers (e.g. CD25, CD69) or formation of intercellular contacts. In addition, we identified a distinct phenotype of regulatory T cells that was linked to ex vivo response independently from T cell frequency at baseline. High expression levels of Aiolos (IKZF1), ICOS and CXCR5 were positively associated with ex vivo response, whereas strong expression of Helios (IKZF2) had unfavorable impact on ex vivo response to BsAb. Furthermore, we demonstrated that lenalidomide, nivolumab and atezolizumab improved ex vivo response to BsAb by potentiating T cell effector functions. In summary, our ex vivo study identifies a distinct regulatory T cell phenotype as potential contributor to treatment failure of BsAb, and suggests drug combinations of high clinical relevance that could improve the efficacy of BsAb.

Prevalence of Allergic Diseases in Children Vaccinated Against Tuberculosis and Hepatitis B in the Early Neonatal Period: Literature Review

2021 ◽  
pp. 420-425
Author(s):  
Marina V. Fedoseenko ◽  
Veronika A. Petrova ◽  
Leyla S. Namazova-Baranova
Keyword(s):  
Immune Response ◽  
Risk Factor ◽  
Hepatitis B ◽  
Neonatal Period ◽  
Allergic Diseases ◽  
T Cell Response ◽  
Response Type ◽  
Early Neonatal Period ◽  
Hepatitis B Vaccines ◽  
Severe Infections

Background. T-cell response is shifted towards Th2-type predominance in newborns. This makes them particularly vulnerable to exposure of various external pathogens, development of severe infections, moreover, it is also a risk factor for allergic diseases development. Various methods of switching the immune response to Th1-type are currently under research, and one of them is vaccination.Objective. The aim of the study is to provide data on the prevalence of allergic pathology among children vaccinated against tuberculosis and hepatitis B, as well as the effect of vaccines on immune response type.Results. Data on both increase and decrease in the prevalence of atopic conditions in children vaccinated with BCG and against hepatitis B were analyzed, thus, most of them cannot be considered reliable. The results of several large studies do not reveal any correlation between vaccination and the presence of allergic disease in children. There is data that BCG and hepatitis B vaccines shift the immune response towards Th1-type activation.Conclusion. Vaccination in the early neonatal period may affect switching of the immune response towards Th1-type. That, in turn, can affect the prevalence of allergic pathology in vaccinated children. However, the data available for now is not sufficient to reliably estimate the possible effect of vaccination on atopic conditions manifestation in the future.

CD4+CD25+ Marrow Infiltrating Lymphocytes in Myeloma Patients Display an Activated Phenotype and Lack Suppressive Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1741-1741
Author(s):  
Kimberly A. Noonan ◽  
Stephanie Mgebroff ◽  
Paolo Serafini ◽  
Kristen Meckel ◽  
Mark Bonyhadi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Cell Phenotype ◽  
Autologous Tumor ◽  
Activation Markers ◽  
Tumor Specificity ◽  
And Function ◽  
Infiltrating Lymphocytes

Abstract We have previously shown that marrow infiltrating lymphocytes (MILs) from myeloma patients proliferate upon stimulation with anti-CD3/CD28 beads more efficiently and exhibit greater specificity to autologous tumor than their peripheral blood lymphocyte (PBL) counterparts. In attempting to dissect the mechanisms responsible for greater tumor specificity of MILs, we examined the frequency and function of the putative CD4+/CD25+ regulatory T cells (Tregs) in both compartments. Phenotypic and functional differences in the CD4+/CD25+ populations were examined in MILs and PBLs from 12 multiple myeloma patients and 3 normal donors. CD4+/CD25+ cells were stained for the suppressive marker: FoxP3; or the activation markers: CD40L, CD71 (transferrin receptor). CD4+/CD25+ MILs of myeloma patients are CD25lo, FoxP3lo and predominantly express activation markers. They expand more readily upon anti-CD3/CD28 stimulation, produce high amounts of the Th1 cytokines: IFNγ and IL-2, and low amounts of IL-10. Importantly, they fail to suppress the tumor specific T cell proliferation. These findings are all consistent with an activated T cell phenotype. In contrast, CD4+/CD25+ cells from PBLs of myeloma patients are CD25hi, FoxP3+, primarily produce IL-10 and IL-4 and markedly suppress T cell expansion in a tumor specific assay, suggestive of a regulatory T cell phenotype. Although MILs possess a lower number of FoxP3+ cells as compared to PBLs, the higher MFI may indicate the presence of a small yet highly regulatory T cell population. Interestingly, MILs from normal donors possess a more regulatory phenotype then their myeloma counterparts as determined by high FoxP3 and low CD40L and CD71 expression as well as reduced expansion upon activation. Taken together, these data underscore major differences in the immuno-inhibitory pathways present in blood as compared to marrow. Notably, MILs of myeloma patients demonstrate a paucity of Tregs. These differences may explain the disparities seen in the tumor-specificity of T cells from these two compartments. The ability to expand a T cell population with fewer endogenous Tregs and heightened tumor-specificity may have significant implications for the implementation of adoptive immunotherapy. %CD25 (MFI) %FoxP3 (MFI) %CD40L %CD71 Fold Expansion Ability to Suppress Myeloma CD4/CD25 MILs 4.7 (29.6) 2.2 (2932.1) 88.8 90.1 12.2 − CD4/CD25 PBLs 19.1 (115.2) 52.3 (163.7) 15.7 19.6 2.5 +++++ Normal CD4/CD25 MILs 14.0 (56.8) 70.1 (82.7) 37.3 6.4 3.3 +++ CD4/CD25 PBLs 24.0 (19.4) 30.9 (261.8) 12.1 4.2 4.0 ++

scholarly journals Passive immunity in lambs: Colostral and serum γ-glutamyltransferase as a predictor of IgG concentration and related to the diseases from birth to 12 weeks of life

2021 ◽  
Vol 66 (No. 2) ◽  
pp. 45-57
Author(s):  
E Gokce ◽  
AH Kirmizigul ◽  
O Atakisi ◽  
M Kuru ◽  
HM Erdogan
Keyword(s):  
Regression Model ◽  
Linear Relationship ◽  
Immunoglobulin G ◽  
Immune Status ◽  
Neonatal Period ◽  
Passive Transfer ◽  
Passive Immunity ◽  
Blood Samples ◽  
Neonatal Lambs

The main goal of this study was to find a link between colostrum and the 1-day-old lamb serum γ-glutamyltransferase (GGT) activity and immunoglobulin G (IgG) concentration and their relation with neonatal diseases and beyond. Further, to set a linear relationship between the serum GGT activity (SGGTA) and the IgG concentration (SIgGC) in different days of the neonatal period, thereby determining the feasibility of the GGT activity in the prediction of the colostrum quality and passive immunity and to define a cut-off point for the SGGTA associated with an increased risk of illness or death in lambs. For this purpose, blood samples were obtained from the lambs before the colostrum intake (day 0) and on different days (1, 2, 4, 7, 14 and 28) in the neonatal period. The colostrum was collected from the respective ewes (n = 254) related to the lambs. The most accurate (R<sup>2</sup> = 0.652) model for predicting the SIgGC or passive immune status was the multiple regression model developed to calculate ln[IgG] from ln[GGT] in healthy neonatal lambs using the serum GGT and IgG values of day 0, 1, 2, 4, 7, 14 and 28. The In[GGT] activity at 24 h after birth in lambs that died or became ill during the neonatal period accounted for approximately 77% and 88% of the variation in the ln[IgG] concentration at 24 h after birth, respectively. The study revealed that SGGTA-24 &gt; 500 IU may be considered as a critical cut-off point for the adequate colostral passive transfer. This study also disclosed that the colostral GGT activity might be used as an indicator to determine the colostrum quality.

scholarly journals Investigation of the response of tear-film neutrophils to interleukin 8 and their sensitivity to centrifugation, fixation, and incubation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yutong Jin ◽  
Lyndon Jones ◽  
Maud Gorbet
Keyword(s):  
Tear Film ◽  
Receptor Expression ◽  
Interleukin 8 ◽  
Polymorphonuclear Neutrophils ◽  
Cell Phenotype ◽  
Cell Integrity ◽  
Activation Markers ◽  
Surface Receptors ◽  
Sterile Phosphate Buffer ◽  
The Impact

AbstractDuring eye closure, a large number of neutrophils (polymorphonuclear neutrophils, PMNs) invade the ocular surface and are often referred to as tear-film PMNs. While immunophenotyping experiments have been performed on tear-film PMNs, the impact of commonly used experimental procedures on their phenotype as well as their response to interleukin-8 (IL-8), a physiological inflammatory mediator, have not yet been investigated. A gentle eye wash method was used to collect cells at home. In the morning upon awaking, participants washed their eyes with sterile phosphate buffer saline (PBS) and collected the runoff into a sterile polypropylene tube. The cell collection was then delivered to the lab within two hours. The effects of centrifugation, incubation and fixation with paraformaldehyde (PFA) before (pre-fixed staining) or after (post-fixed staining) incubation with antibodies were characterized. Tear-film PMNs as well as blood PMNs (used for comparison) were also stimulated with IL-8. To assess the reproducibility of cell collection and variability in receptor expression over time, participants were also asked to collect cells three times over a period of a month. The change in expression of surface receptors, CD11b, CD16, CD55, CD66b, important inflammatory and activation markers, and CD45 (PAN leukocyte marker) was assessed by flow cytometry. Fixing tear-film PMNs prior to the staining with antibodies resulted in a significant (fivefold or more) reduction in the expression of CD11b, CD16 and CD45 when compared to unfixed samples, while CD16 was the only receptor to undergo significant downregulation upon post-staining fixation. Furthermore, additional centrifugation step prior to antibody incubation as well as long (4 h) incubation at 37 °C resulted in significant reductions in expression of CD11b, CD16 and CD55 when compared to control samples. As opposed to blood PMNs, stimulating tear-film PMNs with IL-8 did not induce any significant changes in expression of CD11b, CD16, CD55 and CD66b. When working with collected tear-film PMNs, our results suggest that any additional centrifugation and incubation step should be avoided, or at least limited, and post fixation staining is recommended in order to preserve cell phenotype and cell integrity of tear film PMNs. Our study also adds further information on the reproducibility of the gentle eye wash as well as the inability of tear-film PMNs to modulate their surface receptors upon stimulation with IL-8. The latter may be due to prior exposure to IL-8, activation in the closed-eye environment, or a reduced ability to respond to inflammatory stimulus. Further mechanistic studies will be needed to gain a better understanding of the tear-film neutrophil phenotype.

scholarly journals Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma

Leukemia ◽  
2021 ◽  
Author(s):  
Maria A. Garcia-Marquez ◽  
Martin Thelen ◽  
Sarah Reinke ◽  
Diandra Keller ◽  
Kerstin Wennhold ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
Cellular Therapy ◽  
Effector Memory ◽  
Cell Phenotype ◽  
Line Treatment ◽  
Activation Markers ◽  
Tumor Associated Antigens ◽  
Lymphocyte Phenotype

AbstractWhile classical Hodgkin lymphoma (HL) is highly susceptible to anti-programmed death protein 1 (PD1) antibodies, the exact modes of action remain controversial. To elucidate the circulating lymphocyte phenotype and systemic effects during anti-PD1 1st-line HL treatment we applied multicolor flow cytometry, FluoroSpot and NanoString to sequential samples of 81 HL patients from the NIVAHL trial (NCT03004833) compared to healthy controls. HL patients showed a decreased CD4 T-cell fraction, a higher percentage of effector-memory T cells and higher expression of activation markers at baseline. Strikingly, and in contrast to solid cancers, expression for 10 out of 16 analyzed co-inhibitory molecules on T cells (e.g., PD1, LAG3, Tim3) was higher in HL. Overall, we observed a sustained decrease of the exhausted T-cell phenotype during anti-PD1 treatment. FluoroSpot of 42.3% of patients revealed T-cell responses against ≥1 of five analyzed tumor-associated antigens. Importantly, these responses were more frequently observed in samples from patients with early excellent response to anti-PD1 therapy. In summary, an initially exhausted lymphocyte phenotype rapidly reverted during anti-PD1 1st-line treatment. The frequently observed IFN-y responses against shared tumor-associated antigens indicate T-cell-mediated cytotoxicity and could represent an important resource for immune monitoring and cellular therapy of HL.

scholarly journals Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas

2020 ◽  
Vol 8 (2) ◽  
pp. e001355
Author(s):  
Sean J Judge ◽  
Morgan A Darrow ◽  
Steve W Thorpe ◽  
Alicia A Gingrich ◽  
Edmond F O'Donnell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Soft Tissue ◽  
T Cell Activation ◽  
Ex Vivo ◽  
Unmet Need ◽  
Soft Tissue Sarcomas ◽  
Cell Phenotype ◽  
Activation Markers ◽  
And Function

PurposeGiven the unmet need for novel immunotherapy in soft tissue sarcoma (STS), we sought to characterize the phenotype and function of intratumoral natural killer (NK) and T cells to identify novel strategies to augment tumor-infiltrating lymphocyte (TIL) function.Experimental designUsing prospectively collected specimens from dogs and humans with sarcomas, archived specimens, and The Cancer Genome Atlas (TCGA) data, we evaluated blood and tumor NK and T cell phenotype and function and correlated those with outcome. We then assessed the effects of interleukin 15 (IL-15) stimulation on both NK and T cell activation and TIGIT upregulation. Finally, we evaluated cytotoxic effects of IL-15 combined with TIGIT blockade using a novel anti-TIGIT antibody.ResultsTILs were strongly associated with survival outcome in both archived tissue and TCGA, but higher TIL content was also associated with higher TIGIT expression. Compared with blood, intratumoral NK and T cells showed significantly higher expression of both activation and exhaustion markers, in particular TIGIT. Ex vivo stimulation of blood and tumor NK and T cells from patients with STS with IL-15 further increased both activation and exhaustion markers, including TIGIT. Dogs with metastatic osteosarcoma receiving inhaled IL-15 also exhibited upregulation of activation markers and TIGIT. Ex vivo, combined IL-15 and TIGIT blockade using STS blood and tumor specimens significantly increased cytotoxicity against STS targets.ConclusionIntratumoral NK and T cells are prognostic in STS, but their activation is marked by significant upregulation of TIGIT. Our data suggest that combined IL-15 and TIGIT blockade may be a promising clinical strategy in STS.

scholarly journals Effect of feeding whole compared with cell-free colostrum on calf immune status: The neonatal period

2015 ◽  
Vol 98 (6) ◽  
pp. 3729-3740 ◽  
Author(s):  
S.N. Langel ◽  
W.A. Wark ◽  
S.N. Garst ◽  
R.E. James ◽  
M.L. McGilliard ◽  
...  
Keyword(s):  
Immune Status ◽  
Neonatal Period ◽  
Effect Of Feeding

Quantitative Model-Based Image Analysis of NuMa Distribution Links Nuclear Organization with Cell Phenotype

2001 ◽  
Vol 7 (S2) ◽  
pp. 578-579
Author(s):  
David W. Knowles ◽  
Sophie A. Lelièvre ◽  
Carlos Ortiz de Solόrzano ◽  
Stephen J. Lockett ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Image Analysis ◽  
Mammary Epithelial Cells ◽  
Nuclear Organization ◽  
Critical Role ◽  
Quantitative Model ◽  
Mammary Epithelial ◽  
Cell Phenotype ◽  
Proliferating Cells ◽  
Mitotic Apparatus ◽  
Model Based

The extracellular matrix (ECM) plays a critical role in directing cell behaviour and morphogenesis by regulating gene expression and nuclear organization. Using non-malignant (S1) human mammary epithelial cells (HMECs), it was previously shown that ECM-induced morphogenesis is accompanied by the redistribution of nuclear mitotic apparatus (NuMA) protein from a diffuse pattern in proliferating cells, to a multi-focal pattern as HMECs growth arrested and completed morphogenesis . A process taking 10 to 14 days.To further investigate the link between NuMA distribution and the growth stage of HMECs, we have investigated the distribution of NuMA in non-malignant S1 cells and their malignant, T4, counter-part using a novel model-based image analysis technique. This technique, based on a multi-scale Gaussian blur analysis (Figure 1), quantifies the size of punctate features in an image. Cells were cultured in the presence and absence of a reconstituted basement membrane (rBM) and imaged in 3D using confocal microscopy, for fluorescently labeled monoclonal antibodies to NuMA (fαNuMA) and fluorescently labeled total DNA.

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