scholarly journals Immunological Features of Measles in Children

2021 ◽  
Vol 53 (03) ◽  
pp. 11-15
Author(s):  
Yethindra Vityala ◽  
Keyword(s):  
Immune Deficiency ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Status ◽  
Immunofluorescence Microscopy ◽  
Relative Content ◽  
Effective Vaccine ◽  
Cell Proportion ◽  
Experimental Group

Background: Despite the availability of a safe and effective vaccine, measles remains endemic in many countries and is the main cause of morbidity and mortality among young children. Therefore, the main objective of the study was to investigate the immunological features of measles in children. Materials and Methods: The immune status of children (n = 72) who were diagnosed with measles, was analysed. Various lymphocyte proportions were determined using monoclonal antibodies and immunofluorescence microscopy. The immunoregulatory index was calculated. Results: The relative content of CD4+ and CD8+ T cells in the experimental group comprising of moderately and severely ill patients was significantly lower. The immunoregulatory index was reduced, and there was a positive correlation (0.3) between the indices during admission (2.0469 ± 0.04830) and during the entire hospital stay (1.9258 ± 0.09099) in moderately ill patients, respectively. The proportion of CD16+ T cells was higher at admission and the rate of the increase in CD16+ T cell proportion was significantly higher (P < 0.05). CD16+ counts were higher in moderate to severe cases. Thus, moderately and severely ill children with measles exhibited T-cell immune deficiency. Conclusion: The severity of measles directly correlated with the patient age, with the disease progressing to the severe status in younger children (r = -0.3).

scholarly journals Multi-Dimensional Analysis of Immune Signature Predicts Response to Decitabine Treatment in Elderly Patients with AML

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1526-1526
Author(s):  
Chenchen Zhao ◽  
Bei Jia ◽  
Liru Wang ◽  
David F. Claxton ◽  
W. Christopher Ehmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcome ◽  
Cd8 T Cells ◽  
Immune Status ◽  
Granzyme B ◽  
Cd8 T Cell ◽  
Immune Signature ◽  
Ifn Γ

Abstract Treatment for elderly AML patients who are unfit for intensive chemotherapy remains challenging. Induction with hypomethylating agents (HMA) are the most commonly used approach, however the rate of complete remission (CR) is only around 20% and median survival of 7-12 months. Clearly how to improve the clinical outcome in this patient population is an unmet need. Immunotherapy is promising in cancer treatment. A recent study demonstrated that HMA enhanced PD-1 pathway in MDS and AML patients (Yang et al., Leukemia 2014), suggesting a role of combining HMA and immunotherapy in leukemia therapeutics. To optimize this strategy, it is crucial to understand the interaction between HMA and immune response in AML. Here we performed both phenotypic and functional analysis on clinical samples collected from AML patients undergoing treatment of decitabine (DAC), a broadly used HMA. We aim to determine 1) how DAC influences the immune system; and 2) whether the immune status in AML patients predict the response to DAC treatment. Total of 22 peripheral blood samples from 11 AML patients receiving DAC were examined. Samples were collected at the time of prior to and 1-month post DAC treatment. We conducted a comprehensive phenotypic analysis of immune markers characterizing each immune component (T cells, B cells, NK, NKT, monocytes, myeloid-derived suppressor cells, and dendritic cells) and expression patterns of co-stimulatory or inhibitory molecules. In addition, perforin, granzyme B and cytokine release in response to anti-CD3/CD28 stimulation were examined to determine the functional status of T cells. A total of 45 markers separated in 8 overlapped staining panels were tested by flow cytometry. We first assessed the impact of DAC on the immune response in AML. Comparing the paired samples prior to vs. post treatment from the same patients, we observed an increase of the percentage of NK cells, as well as their expression of granzyme B and perforin upon DAC treatment. In contrast, DAC appears to cause CD8 T cell suppression as CD8 T cells from post-DAC samples showed higher PD-1 expression whereas lower IFN-γ production. We next investigated the predictive value of immune status for the response to DAC treatment. Among the 18 evaluable samples, we defined 10 responders (CR/Cri/PR) vs. 8 non-responders (treatment failure) based on the ELN 2017 recommendations. The correlation of immune characteristics to the clinical response was carefully examined. We started with an unsupervised principal component analysis (PCA), which revealed a distinguished pattern between the responders and non-responders (Fig. 1A). This encouraging observation suggests an association of immune signature to clinical outcome. Subsequent analysis demonstrated a major contribution of CD8 T cells to the association. We then focused on the phenotypic and functional analysis of CD8 T cells in responders vs. non-responders. We found a significantly higher percentage of terminal differentiated cells in non-responders compared with that of responders. Importantly, in the perspective of phenotypes, hierarchical clustering on markers of CD8 T cells divided samples into two major clades, 7 of 8 samples (87.5%) were responders on one branch and 7 of 10 samples (70%) were non-responders on the other. Most responders expressed lower frequency of inhibitory receptors and higher frequency of stimulatory receptors, whereas non-responders showed the opposite trend (Fig. 1B). The significant difference of these receptors was validated in paired t test analysis. Functional studies also showed more IFN-γ production in responders. Interestingly the intracellular staining of perforin and granzyme B was higher in non-responders, likely due to exhausted T cells that are unable to release these particles extracellularly. Collectively, our study discovered the vital role of the immune signature in predicting clinical outcome in AML. High functional CD8 T cell status, manifested by more capability of IFN-γ production, enhanced stimulatory molecule and low inhibitory receptor expression, associated with effective clinical response to DAC treatment. In addition, CD8 T cell function was down-regulated upon DAC treatment. Our results provide a strong rationale for integrating immunotherapy into HMA treatment in AML, also highlight the importance of immune signature analysis in the future trial design for this clinical setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals In silico construction of a multiepitope Zika virus vaccine using immunoinformatics tools

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ana Clara Barbosa Antonelli ◽  
Vinnycius Pereira Almeida ◽  
Fernanda Oliveira Feitosa de Castro ◽  
Jacyelle Medeiros Silva ◽  
Irmtraut Araci Hoffmann Pfrimer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Zika Virus ◽  
In Silico ◽  
Protein Domain ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Zikv Infection ◽  
Acute Neuropathy

AbstractZika virus (ZIKV) is an arbovirus from the Flaviviridae family and Flavivirus genus. Neurological events have been associated with ZIKV-infected individuals, such as Guillain-Barré syndrome, an autoimmune acute neuropathy that causes nerve demyelination and can induce paralysis. With the increase of ZIKV infection incidence in 2015, malformation and microcephaly cases in newborns have grown considerably, which suggested congenital transmission. Therefore, the development of an effective vaccine against ZIKV became an urgent need. Live attenuated vaccines present some theoretical risks for administration in pregnant women. Thus, we developed an in silico multiepitope vaccine against ZIKV. All structural and non-structural proteins were investigated using immunoinformatics tools designed for the prediction of CD4 + and CD8 + T cell epitopes. We selected 13 CD8 + and 12 CD4 + T cell epitopes considering parameters such as binding affinity to HLA class I and II molecules, promiscuity based on the number of different HLA alleles that bind to the epitopes, and immunogenicity. ZIKV Envelope protein domain III (EDIII) was added to the vaccine construct, creating a hybrid protein domain-multiepitope vaccine. Three high scoring continuous and two discontinuous B cell epitopes were found in EDIII. Aiming to increase the candidate vaccine antigenicity even further, we tested secondary and tertiary structures and physicochemical parameters of the vaccine conjugated to four different protein adjuvants: flagellin, 50S ribosomal protein L7/L12, heparin-binding hemagglutinin, or RS09 synthetic peptide. The addition of the flagellin adjuvant increased the vaccine's predicted antigenicity. In silico predictions revealed that the protein is a probable antigen, non-allergenic and predicted to be stable. The vaccine’s average population coverage is estimated to be 87.86%, which indicates it can be administered worldwide. Peripheral Blood Mononuclear Cells (PBMC) of individuals with previous ZIKV infection were tested for cytokine production in response to the pool of CD4 and CD8 ZIKV peptide selected. CD4 + and CD8 + T cells showed significant production of IFN-γ upon stimulation and IL-2 production was also detected by CD8 + T cells, which indicated the potential of our peptides to be recognized by specific T cells and induce immune response. In conclusion, we developed an in silico universal vaccine predicted to induce broad and high-coverage cellular and humoral immune responses against ZIKV, which can be a good candidate for posterior in vivo validation.

T cell receptor activation status as biological context for interpreting PD1/PDL1 biomarker measurements.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 54-54
Author(s):  
Ralph E. Parchment ◽  
Tony Navas ◽  
Kristin Fino ◽  
Andy Fung ◽  
Facundo Cutuli ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immunofluorescence Microscopy ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Tcr Activation

54 Background: Direct cytolysis of tumor cells by CD8+ T cells results from the net effect of at least two biochemical pathways: (1) stimulatory signaling from the activated T cell receptor (TCR) complex in response to its recognition of a tumor neoantigen presented in the context of autologous MHC class I, and (2) suppressive signaling from immune checkpoints, such as the response of PD1 to binding its ligand, PDL1. Because the PD1:PDL1 immune checkpoint is significant for therapy only when there is tumor cell-specific TCR activation and signaling, it is not surprising that simple measurements of either PD1 or PDL1 in tumor biopsies are, at best, imperfect predictive biomarkers. Instead, a more precise test that quantifies PD1 signaling due to PDL1 binding only in the subset of CD8+ T cells exhibiting activated TCR signaling should provide a more accurate assessment of the extent of immune checkpoint suppression of tumor immunity and therefore be a more predictive biomarker of response to PD1/PDL1-targeted immunotherapy. Methods: We have developed a multiplexed immunofluorescence microscopy test capable of simultaneous quantitation of TCR activation (phospho-CD3zeta), immune checkpoint signaling via PD1 (phospho-SHP1 and -SHP2), and the net stimulation or inhibition resulting from the integration of these two pathways (phospho-ZAP70). Results: Specific antibodies to these biomarkers have been qualified, including peptide inhibition studies to establish antibody specificity, and their performance established by fit-for-purpose studies of in vitro models of CD8+ T cell activation. This multiplex biomarker panel is suitable for clinical use with formalin-fixed, paraffin embedded core needle biopsies of tumor and quantitative immunofluorescence microscopy (qIFA). Conclusions: The additional biomarkers of tumor immunity are expected to add an important context for interpreting PD1/PDL1 measurements. Funded by NCI Contract No. HHSN261200800001E.

Peripheral T Cell Apoptosis Is Associated with Homeostatic T Cell Proliferation and Plays a Significant Role in Post-Transplant Immune Deficiency.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 71-71
Author(s):  
Onder Alpdogan ◽  
Neel Patel ◽  
David Suh ◽  
Jeremy Grubin ◽  
Suzanne McGoldrick ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Apoptosis ◽  
T Cell Proliferation ◽  
Post Transplant ◽  
T Cell Apoptosis

Abstract Post-transplant peripheral T cell apoptosis is an important (but ill-defined) contributor to the delay in T cell recovery after an allogeneic bone marrow transplantation (BMT). Using murine bone marrow transplantation (BMT) models to analyze post-transplant peripheral T cell apoptosis, we found that donor BM-derived T cells had a higher percentage of apoptotic cells, with decreased BCL-2 levels in young (3-month old) and old (20-month old) recipients of T cell-depleted (TCD) and T cell-repleted allogeneic BMT. Allogeneic recipients of donor BM deficient of Fas, BAX and TRAIL, or with overexpression of BCL-2 and AKT showed no decrease in donor-derived apoptotic T cells, suggesting that these molecules are not directly responsible for post-transplant peripheral T cell apoptosis. However, we noted that both CD4+ and CD8+ Memory T cells (CD44high) exhibited increased apoptosis when compared to naive T cells post-BMT and therefore used RAG-2-eGFP transgenic mice to study whether T cell maturation affects peripheral T cell apoptosis. We found increased numbers of apoptotic cells in mature (eGFPlow) T cells compared to non-divided (eGFPhigh) recent thymic emigrants in RAG-2-eGFP transgenic mice and in recipients of RAG-2-eGFP transgenic (Tg) BM. Interestingly, most of the apoptotic T cells were of eGFPlowCD44high memory phenotype in both CD4+ and CD8+ T cells, while eGFPlowCD44low naive T cells showed no sign of enhanced apoptosis. Moreover, we found similar increased levels of apoptosis of homeostatically proliferating T cells (CD44high-memory-like cells) in recipients of lineage-depleted allogeneic RAG2-eGFP Tg BM or B6 BM. We then tested the effects of homeostatic T cell proliferation on peripheral T cell apoptosis in recipients of syngeneic CFSE-labeled T cells and found again increased levels of apoptosis in the fast proliferating populations of both CD4+ and CD8+ T cells. These cells expressed high levels of CD44 but down-regulated CD62L on their surface and in contrast to allogeneic proliferation exhibited low levels of CD25 expression and high level of IL-7Rα expression (75%). In addition, BCL-2 expression was down-regulated in the fast-proliferating cell population in both CD4+ and CD8+ T cells. We conclude that newly generated donor BM-derived T cells have increased peripheral T cell apoptosis, which is associated with homeostatic proliferation and does not involve Fas, BAX, TRAIL, and AKT. This mechanism of peripheral T cell apoptosis, which has not been recognized previously, plays a significant role in post-transplant T cell deficiency and represents a promising target for novel strategies to overcome post-transplant immune deficiency in BMT recipients.

CD8 T cells are not required for islet destruction induced by a CD4+ islet-specific T-cell clone

Diabetes ◽  
1992 ◽  
Vol 41 (12) ◽  
pp. 1603-1608 ◽  
Author(s):  
B. J. Bradley ◽  
K. Haskins ◽  
F. G. La Rosa ◽  
K. J. Lafferty
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Clone ◽  
T Cell Clone
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