scholarly journals Early Gamma Interferon and Interleukin-2 Responses to Vaccination Predict the Late Resting Memory in Malaria-Naïve and Malaria-Exposed Individuals

2006 ◽  
Vol 74 (11) ◽  
pp. 6331-6338 ◽  
Author(s):  
Philip Bejon ◽  
Sheila Keating ◽  
Jedidah Mwacharo ◽  
Oscar K. Kai ◽  
Susanna Dunachie ◽  
...  

ABSTRACT Two different cell populations respond to potent T-cell-inducing vaccinations. The induction and loss of effector cells can be seen using an ex vivo enzyme-linked immunospot (ELISPOT) assay, but the more durable resting memory response is demonstrable by a cultured ELISPOT assay. The relationship of the early effector response to durable resting memory is incompletely understood. Effector phenotype is usually identified by gamma interferon (IFN-γ) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-γ- and IL-2-secreting effector cells were identified by an ex vivo ELISPOT assay 1 week after vaccination and compared with the resting memory responses detected by a cultured ELISPOT assay 3 months later. The different kinetics and induction of IL-2 by different vaccines and natural exposure are described. Furthermore, both early IFN-γ and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-naïve volunteers, but only IFN-γ predicted memory in malaria-exposed volunteers. However, dual ELISPOT assays were also performed on malaria-exposed volunteers to identify cells producing both cytokines simultaneously. This demonstrated that double-cytokine-producing cells were highly predictive of memory. This assay may be useful in predicting vaccinations most likely to generate stable, long-term memory responses.

2000 ◽  
Vol 7 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Tadao Asai ◽  
Walter J. Storkus ◽  
Theresa L. Whiteside

ABSTRACT Frequencies of vaccine-responsive T-lymphocyte precursors in peripheral blood mononuclear cells (PBMC) prior to and after administration of peptide-based vaccines in patients with cancer can be measured by limiting-dilution assays (LDA) or by ELISPOT assays. We have used a modified version of the ELISPOT assay to monitor changes in the frequency of gamma interferon (IFN-γ)-producing T cells in a population of lymphocytes responding to a relevant peptide or a nonspecific stimulator, such as phorbol myristate acetate-ionomycin. Prior to its use for monitoring of patient samples, the assay was validated and found to be comparable to the LDA performed in parallel, using tumor-reactive cytolytic T-lymphocyte (CTL) lines. The sensitivity of the ELISPOT assay was found to be 1/100,000 cells, with an interassay coefficient of variation of 15%, indicating that it could be reliably used for monitoring of changes in the frequency of IFN-γ-secreting responder cells in noncultured or cultured lymphocyte populations. To establish that the assay is able to detect the T-cell precursor cells responsive to the vaccine, we used CD8+T-cell populations positively selected from PBMC of HLA-A2+patients with metastatic melanoma, who were treated with dendritic cell-based vaccines containing gp100, MELAN-A/MART-1, tyrosinase, and influenza virus matrix peptides. The frequency of peptide-specific responder T cells ranged from 0 to 1/2,600 before vaccination and increased by at least 1 log unit after vaccination in two patients, one of whom had a clinical response to the vaccine. However, no increases in the frequency of peptide-responsive T cells were observed in noncultured PBMC or PBMC cultured in the presence of the relevant peptides after the melanoma patients enrolled in another trial were treated with the intramuscular peptide vaccine plus MF59 adjuvant. Thus, while the ELISPOT assay was found to be readily applicable to assessments of frequencies of CTL precursors of established CTL lines and ex vivo-amplified PBMC, its usefulness for monitoring of fresh PBMC in patients with cancer was limited. In many of these patients antitumor effector T cells are present at frequencies of lower than 1/100,000 in the peripheral circulation. Serial monitoring of such patients may require prior ex vivo amplification of specific precursor cells.


2005 ◽  
Vol 79 (6) ◽  
pp. 3243-3253 ◽  
Author(s):  
Shanmugalakshmi Sadagopal ◽  
Rama Rao Amara ◽  
David C. Montefiori ◽  
Linda S. Wyatt ◽  
Silvija I. Staprans ◽  
...  

ABSTRACT In 2001, we reported 20 weeks of control of challenge with the virulent 89.6P chimera of simian and human immunodeficiency viruses (SHIV-89.6P) by a Gag-Pol-Env vaccine consisting of DNA priming and modified vaccinia virus Ankara boosting. Here we report that 22 out of 23 of these animals successfully controlled their viremia until their time of euthanasia at 200 weeks postchallenge. At euthanasia, all animals had low to undetectable viral loads and normal CD4 counts. During the long period of viral control, gamma interferon (IFN-γ)-producing antiviral T cells were present at unexpectedly low breadths and frequencies. Most animals recognized two CD8 and one CD4 epitope and had frequencies of IFN-γ-responding T cells from 0.01 to 0.3% of total CD8 or CD4 T cells. T-cell responses were remarkably stable over time and, unlike responses in most immunodeficiency virus infections, maintained good functional characteristics, as evidenced by coproduction of IFN-γ and interleukin-2. Overall, high titers of binding and neutralizing antibody persisted throughout the postchallenge period. Encouragingly, long-term control was effective in macaques of diverse histocompatibility types.


2002 ◽  
Vol 76 (24) ◽  
pp. 12414-12422 ◽  
Author(s):  
Florence Buseyne ◽  
Daniel Scott-Algara ◽  
Françoise Porrot ◽  
Béatrice Corre ◽  
Nassima Bellal ◽  
...  

ABSTRACT HIV-specific CD8+ T cells are critical in controlling human immunodeficiency virus (HIV) replication. We present the evaluation of a gamma-interferon (IFN-γ)-based enzyme linked immunospot (ELISPOT) assay for the quantification of HIV-specific CD8+ T cells from HIV-infected children. We studied 20 HLA-A∗0201-positive HIV-infected children. The IFN-γ production in response to stimulation with two HLA-A∗0201-restricted immunodominant CD8 epitopes (SLYNTVATL [SL9] in Gag and ILKEPVHGV [IV9] in Pol) was tested using the ELISPOT assay. The results were compared to labeling with the corresponding tetramers. Among the 20 children, 18 had detectable responses against the SL9 and/or the IV9 epitope using the ELISPOT assay (medians, 351 and 134 spot-forming cells/106 peripheral blood mononuclear cells, respectively). Comparison of results from the tetramer and ELISPOT assays suggests that only a fraction of HIV-specific CD8+ T cells were able to produce IFN-γ. Most importantly, we found that the frequencies of IFN-γ-producing CD8+ T cells were positively correlated with the viral load whereas the frequencies of tetramer-binding CD8+ T cells were not. The high sensitivity of the ELISPOT assay and the fact that this functional assay provided information different from that of tetramer labeling support its use for measurement of HIV-specific CD8+ T cells. In conclusion, our results show that the ex vivo-activated IFN-γ-producing HIV-specific CD8+-T-cell subset is dependent upon continuous antigenic stimulation.


2003 ◽  
Vol 26 (6) ◽  
pp. 759-760
Author(s):  
Sabine Weiss ◽  
Horst M. Mueller

In their target article, Ruchkin et al. propose sustained neuronal interaction of prefrontal and posterior cortex involved in memory-storage mechanisms with respect to electrophysiological findings on the relationship of short-term and long-term memory processes. We will evaluate this claim in light of recent evidence from our laboratory on EEG coherence analysis of memory processes accompanying language comprehension.


2010 ◽  
Vol 17 (9) ◽  
pp. 1305-1314 ◽  
Author(s):  
Rosângela Salerno-Goncalves ◽  
Rezwanul Wahid ◽  
Marcelo B. Sztein

ABSTRACT T cells are likely to play an important role in the host defense against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. We have shown that HLA-E can function as a restriction element for S. Typhi-specific CD8+ T cells. Because of the potential importance of HLA-E-restricted CD8+ responses in resistance to Salmonella infection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine. Cells were obtained from volunteers before and at days 2, 4, 7, 10, 14, 28, 42, 56, 120, 180, 360, and 720 after immunization. An ex vivo multicolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was used to functionally assess memory T-cell subsets by flow cytometry. Increases in cytokine-secreting CD8+ cells were observed in the T effector/memory (TEM) and CD45RA+ TEM (TEMRA) subsets as early as 4 days after immunization and persisted, particularly in the TEMRA subset, up to 2 years after immunization. The majority of HLA-E-restricted CD8+ cells 28 to 56 days after immunization coexpressed CD107, IFN-γ, and TNF-α, showing characteristic features of multifunctional T cells. In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity to S. Typhi. Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8+ cells after immunization.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Mao ◽  
Jun Kang Chow ◽  
Pin Siang Tan ◽  
Kuan-fu Liu ◽  
Jimmy Wu ◽  
...  

AbstractAutomatic bird detection in ornithological analyses is limited by the accuracy of existing models, due to the lack of training data and the difficulties in extracting the fine-grained features required to distinguish bird species. Here we apply the domain randomization strategy to enhance the accuracy of the deep learning models in bird detection. Trained with virtual birds of sufficient variations in different environments, the model tends to focus on the fine-grained features of birds and achieves higher accuracies. Based on the 100 terabytes of 2-month continuous monitoring data of egrets, our results cover the findings using conventional manual observations, e.g., vertical stratification of egrets according to body size, and also open up opportunities of long-term bird surveys requiring intensive monitoring that is impractical using conventional methods, e.g., the weather influences on egrets, and the relationship of the migration schedules between the great egrets and little egrets.


2021 ◽  
pp. 105477382110381
Author(s):  
Kelly Haskard-Zolnierek ◽  
Courtney Wilson ◽  
Julia Pruin ◽  
Rebecca Deason ◽  
Krista Howard

Individuals with hypothyroidism suffer from symptoms including impairments to cognition (i.e., “brain fog”). Medication can help reduce symptoms of hypothyroidism; however, brain fog may hinder adherence. The aim of this study was to determine if memory impairment and cognitive failures are related to treatment nonadherence in 441 individuals with hypothyroidism. Participants with a diagnosis of hypothyroidism and currently prescribed a thyroid hormone replacement medication were placed in two groups according to adherence level and compared on validated scales assessing impairments to memory and cognition. Results indicated a significant association between treatment nonadherence and self-reported brain fog, represented by greater cognitive and memory impairments. Nonadherent individuals indicated impairments with prospective, retrospective, and short- and long-term memory; and more cognitive failures, compared to adherent individuals. Findings suggest the importance of interventions to enhance adherence for individuals with brain fog, such as encouraging the use of reminders.


1978 ◽  
Vol 16 (4) ◽  
pp. 549-564 ◽  
Author(s):  
J. W. Garmany

This article discusses some of the issues involved in the choice of technology in developing countries, especially those in Africa, and the relationship of this to employment and output. The problem is to find an optimum combination of productive resources that comes nearest to satisfying two objectives: the full and economically efficient utilisation of such resources, and the creation of as much surplus as possible over current consumption, thereby making possible new investment and long-term growth.


2014 ◽  
Vol 4 (3) ◽  
pp. 368 ◽  
Author(s):  
Roshana Gul

Though a lot of studies have been done to conclude customer loyalty as dependent variable but still there is a vast margin of researches to be conducted in future in different spheres of this construct. On the other hand the truth of the importance of customer loyalty as an enduring asset cannot be falsified. It is fundamental for organizations to build up long term and mutual beneficial associations with the customers. The purpose of this research paper is to show the inter relationship of reputation, customer satisfaction and trust on customer loyalty. According to the observations reputation is the major independent variable that has significant relationship with customer satisfaction, customer loyalty, and trust. Data for this research study was taken from the Islamia University, Quaid-e-Azam Medical College, and different banks located at various geographic locations of Bahawalpur region of Pakistan. Data was collected through self administered questionnaire and analyzed by using regression through SPSS. The results have been drawn from 150 users of NISHAT LINEN and it was found that there is positive and significant relationship among reputation, customer satisfaction, trust and customer loyalty. Hence the studies give the positive sign that with the increment of reputation, customer satisfaction and trust the customer loyalty enhances.  


2009 ◽  
Vol 5 (S267) ◽  
pp. 103-103
Author(s):  
A. H. Andrei ◽  
S. Bouquillon ◽  
J. L. Penna ◽  
F. Taris ◽  
S. Anton ◽  
...  

Quasars are the choicest objects to define a quasi-inertial reference frame. At the same time, they are active galactic nuclei powered by a massive black hole. As the astrometric precision of ground-based optical observations approaches the limit set by the forthcoming GAIA mission, astrometric stability can be investigated. Though the optical emission from the core region usually exceeds the other components by a factor of a hundred, the variability of those components must surely imply some measure of variability of the astrometric baricenter. Whether this is confirmed or not, it puts important constraints on the relationship of the quasar's central engine to the surrounding distribution of matter. To investigate the correlation between long-term optical variability and what is dubbed as the “random walk” of the astrometric center, a program is being pursued at the WFI/ESO 2.2m. The sample was selected from quasars known to undergo large-amplitude and long-term optical variations (Smith et al. 1993; Teerikorpi 2000). The observations are typically made every two months. The treatment is differential, comparing the quasar position and brightness against a sample of selected stars for which the average relative distances and magnitudes remain constant. The provisional results for four objects bring strong support to the hypothesis of a relationship between astrometric and photometric variability. A full account is provided by Andrei et al. (2009).


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