scholarly journals Long-term maintenance of human nai ve T cells through in situ homeostasis in lymphoid tissue sites

2016 ◽  
Vol 1 (6) ◽  
pp. eaah6506-eaah6506 ◽  
Author(s):  
J. J. C. Thome ◽  
B. Grinshpun ◽  
B. V. Kumar ◽  
M. Kubota ◽  
Y. Ohmura ◽  
...  
Keyword(s):  
T Cells ◽  
Lymphoid Tissue ◽  
Term Maintenance

scholarly journals Atmospheric CO2, CH4, and CO with CRDS technique at the Izaña Global GAW station: instrumental tests, developments and first measurement results

2017 ◽  
Author(s):  
Angel J. Gomez-Pelaez ◽  
Ramon Ramos ◽  
Emilio Cuevas ◽  
Vanessa Gomez-Trueba ◽  
Enrique Reyes
Keyword(s):  
Drift Rate ◽  
Inlet Pressure ◽  
Response Functions ◽  
Measurement Results ◽  
Ambient Measurements ◽  
Acceptance Tests ◽  
Term Maintenance

Abstract. At the end of 2015, a CO2/CH4/CO Cavity Ring-Down Spectrometer (CRDS) was installed at the Izaña Global Atmosphere Watch station (Tenerife, Spain) to improve the Izaña Greenhouse gases GAW measurement programme, and to guarantee the renewal of the instrumentation and the long-term maintenance of this programme. We present the results of the CRDS acceptance tests, the processing of raw data applied through novel numerical codes, and the response functions used. Also, the calibration results, the implemented water vapour correction, the target gas injection statistics, the ambient measurements performed from December 2015 to July 2017, and their comparison with other continuous in situ measurements are described. The agreement with other in situ continuous measurements is good most of the time for CO2 and CH4, but for CO is just outside the GAW 2-ppb objective. It seems the disagreement is not produced by significant drifts in the CRDS CO WMO tertiary standards. The main novelties are: 1) determination of a slight CO2 correction that takes into account changes in the inlet pressure/flow rate; 2) detailed justification of the use of virtual tanks to monitor the response function changes in time; 3) drift rate determination for the pressure and temperature sensors located inside the CRDS cavity; 4) novelties in the determination of the H2O correction for CO; and 5) determination and discussion of the origin of the CRDS-flow inlet pressure and H2O dependences.

scholarly journals Differential Requirements for T Cells in Viruslike Particle- and Rotavirus-Induced Protective Immunity

2008 ◽  
Vol 82 (6) ◽  
pp. 3135-3138 ◽  
Author(s):  
Sarah E. Blutt ◽  
Kelly L. Warfield ◽  
Mary K. Estes ◽  
Margaret E. Conner
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Protective Immunity ◽  
Short Term ◽  
Correlates Of Protection ◽  
Viruslike Particles ◽  
Term Maintenance ◽  
B And T Lymphocytes

ABSTRACT Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4+ T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered.

scholarly journals Regulating immune memory and reversing tumor thermotolerance through a step-by-step starving-photothermal therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lihua Luo ◽  
Bing Qin ◽  
Mengshi Jiang ◽  
Lin Xie ◽  
Zhenyu Luo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Photothermal Therapy ◽  
Cd8 T Cell ◽  
Immune Memory ◽  
In Situ Vaccine

Abstract Background Photothermal therapy (PTT) is a highly effective treatment for solid tumors and can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+ T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+ Teff) into central memory CD8+ T cell (CD8+ TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, conferring additional protection against the host immune response mediated by PTT. Methods Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME. Results We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+ TCMs were produced and more effective anti-tumor was presented in this study. Conclusion The Step-by-Step starving-photothermal therapy could not only reverse the tumor thermotolerance, but also enhance the ICD and produce more CD8+ TCM during the treatment. Graphical Abstract

scholarly journals Long-Term Maintenance of Virus-Specific Effector Memory CD8+T Cells in the Lung Airways Depends on Proliferation

2002 ◽  
Vol 169 (9) ◽  
pp. 4976-4981 ◽  
Author(s):  
Robert J. Hogan ◽  
Linda S. Cauley ◽  
Kenneth H. Ely ◽  
Tres Cookenham ◽  
Alan D. Roberts ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Specific Effector ◽  
Lung Airways ◽  
Term Maintenance

scholarly journals In Situ Characterization of Human Lymphoid Tissue Immune Cells by Multispectral Confocal Imaging and Quantitative Image Analysis; Implications for HIV Reservoir Characterization

2021 ◽  
Vol 12 ◽  
Author(s):  
Eirini Moysi ◽  
Perla M. Del Rio Estrada ◽  
Fernanda Torres-Ruiz ◽  
Gustavo Reyes-Terán ◽  
Richard A. Koup ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Lymphoid Tissue ◽  
Immune Cell ◽  
Hiv Reservoir ◽  
Human Lymphoid Tissue

CD4 T cells are key mediators of adaptive immune responses during infection and vaccination. Within secondary lymphoid organs, helper CD4 T cells, particularly those residing in germinal centers known as follicular helper T cells (Tfh), provide critical help to B-cells to promote their survival, isotype switching and selection of high affinity memory B-cells. On the other hand, the important role of Tfh cells for the maintenance of HIV reservoir is well documented. Thus, interrogating and better understanding the tissue specific micro-environment and immune subsets that contribute to optimal Tfh cell differentiation and function is important for designing successful prevention and cure strategies. Here, we describe the development and optimization of eight multispectral confocal microscopy immunofluorescence panels designed for in depth characterization and immune-profiling of relevant immune cells in formalin-fixed paraffin-embedded human lymphoid tissue samples. We provide a comprehensive library of antibodies to use for the characterization of CD4+ T-cells -including Tfh and regulatory T-cells- as well as CD8 T-cells, B-cells, macrophages and dendritic cells and discuss how the resulting multispectral confocal datasets can be quantitatively dissected using the HistoCytometry pipeline to collect information about relative frequencies and immune cell spatial distributions. Cells harboring actively transcribed virus are analyzed using an in-situ hybridization assay for the characterization of HIV mRNA positive cells in combination with additional protein markers (multispectral RNAscope). The application of this methodology to lymphoid tissues offers a means to interrogate multiple relevant immune cell targets simultaneously at increased resolution in a reproducible manner to guide CD4 T-cell studies in infection and vaccination.

scholarly journals Regulating Immune Memory and Reversing Tumor Thermotolerance through a Step-by-Step Starving-Photothermal therapy

2021 ◽  
Author(s):  
Lihua Luo ◽  
Bing Qin ◽  
Mengshi Jiang ◽  
Lin Xie ◽  
Zhenyu Luo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Photothermal Therapy ◽  
Aerobic Glycolysis ◽  
Cd8 T Cell ◽  
Immune Memory

Abstract Background: Photothermal therapy (PTT) is a highly effective treatment for solid tumorsand can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+Teff) into central memory CD8+ T cell (CD8+TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, confering additional protection against the host immune response mediated by PTT.Methods: Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+T cells by activating AMPK, increases the number of CD8+TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME.Results: We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+TCMs were produced and more effective anti-tumor was presented in this study.Conclusion: The Step-by-Step starving-photothermal therapy could not only reverse thetumor thermotolerance, but also enhance the ICD and produce more CD8+TCM during the treatment.

Improving efficacy of PD-1 blockade in unresponsive lymphoma tumors with in situ vaccination through induction of a highly efficient cross-presenting dendritic cell subset.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 76-76
Author(s):  
Linda Hammerich ◽  
Maxime Dhainaut ◽  
Thomas A. Davis ◽  
Tibor Keler ◽  
Andres M. Salazar ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Tumor Regression ◽  
Low Grade ◽  
Dendritic Cell Subset ◽  
Term Survival ◽  
Intratumoral Injections

76 Background: Low-grade non-Hodgkin’s B-cell lymphomas are generally incurable; preliminary results with anti-PD-1 therapy have yielded low response rates. Tumoral DC infiltration correlates with efficacy of checkpoint blockade and tumor-targeted vaccines represent promising, novel treatment strategies to induce anti-tumor T cells. Methods: A20 lymphoma-bearing mice were treated with a PD-1 blocking antibody with an in situ vaccine (ISV) consisting of intratumoral injections of FMS-like tyrosine kinase-3 ligand (Flt3L), local irradiation (XRT) of the tumor and intratumoral injections of the TLR3 agonist poly-ICLC (pIC). Results: Untreated lymphoma tumors contained very low numbers of DC and treatment with anti-PD1 alone did not induce tumor regression or increase survival. Flt3L treatment resulted in a dramatic increase of IRF8+TLR3+ DC at the tumor site, the draining lymph node and the spleen. XRT of A20 cells induced activation of Flt3L-treated splenic DC in vitro and local XRT of the tumor in vivo induced expression of CD103 on infiltrating TLR3+ DC. Local XRT also enhanced uptake of dying tumor cells by DC. Interestingly, tumor antigens were taken up mainly by CD103+ DC and not CD103- subtypes. CD103+ expression distinguishes a subset of migratory cross-presenting DC. Accordingly, CD103+ DC isolated from the tumor induced proliferation of tumor-specific CD8+ T cells more efficiently than CD103- subsets. The combination of Flt3L with XRT and pIC induced tumor-reactive, IFNg-producing T cells, but delayed tumor growth and improved survival only in 40% of mice. ISV also increased expression of PD-L1 on tumor cells and tumor infiltrating DC. Consistently, combination of ISV with PD-1 blockade led to complete tumor regression and increased long-term survival in the majority of mice. PD-1 blockade also increased the number of tumor-reactive T cells and depletion of CD8+ T cells abrogated the anti-tumor effect. Conclusions: In situ vaccination can improve efficacy of anti-PD-1 in checkpoint-unresponsive lymphoma tumors through induction of a cross-presenting DC subset leading to long-term regression of established lymphoma tumors.

Sign in / Sign up

Export Citation Format

Share Document