cell memory
Recently Published Documents


TOTAL DOCUMENTS

970
(FIVE YEARS 206)

H-INDEX

92
(FIVE YEARS 11)

2022 ◽  
Vol 12 ◽  
Author(s):  
Vincenzo Barnaba

Long-term immunological memory represents a unique performance of the adaptive immunity selected during evolution to support long-term survival of species in vertebrates, through protection against dangerous “invaders”, namely, infectious agents or unwanted (e.g., tumor) cells. The balance between the development of T cell memory and various mechanisms of immunoregulation (namely, T cell effector exhaustion and regulatory T cell suppression) dictates the fate in providing protection or not in different conditions, such as (acute or chronic) infection, vaccination, cancer, and autoimmunity. Here, these different environments are taken in consideration to outline the up-to-date cellular and molecular features regulating the development or damping of immunological memory and to delineate therapeutic strategies capable to improve or control it, in order to address pathological contexts, such as infection, tumor, and autoimmunity.


2021 ◽  
Vol 23 (1) ◽  
pp. 37
Author(s):  
Anjuman Ara ◽  
Aizhang Xu ◽  
Khawaja Ashfaque Ahmed ◽  
Scot C. Leary ◽  
Md. Fahmid Islam ◽  
...  

Energy sensors mTORC1 and AMPKα1 regulate T-cell metabolism and differentiation, while rapamycin (Rapa)-inhibition of mTORC1 (RIM) promotes T-cell memory. However, the underlying pathway and the role of AMPKα1 in Rapa-induced T-cell memory remain elusive. Using genetic and pharmaceutical tools, we demonstrate that Rapa promotes T-cell memory in mice in vivo post Listeria monocytogenesis rLmOVA infection and in vitro transition of effector T (TE) to memory T (TM) cells. IL-2- and IL-2+Rapa-stimulated T [IL-2/T and IL-2(Rapa+)/T] cells, when transferred into mice, differentiate into short-term IL-7R−CD62L−KLRG1+ TE and long-lived IL-7R+CD62L+KLRG1− TM cells, respectively. To assess the underlying pathways, we performed Western blotting, confocal microscopy and Seahorse-assay analyses using IL-2/T and IL-2(Rapa+)/T cells. We determined that IL-2(Rapa+)/T cells activate transcription FOXO1, TCF1 and Eomes and metabolic pAMPKα1(T172), pULK1(S555) and ATG7 molecules and promote mitochondrial biogenesis and fatty-acid oxidation (FAO). We found that rapamycin-treated AMPKα-deficient AMPKα1-KO IL-2(Rapa+)/TM cells up-regulate transcription factor HIF-1α and induce a metabolic switch from FAO to glycolysis. Interestingly, despite the rapamycin treatment, AMPKα-deficient TM cells lost their cell survival capacity. Taken together, our data indicate that rapamycin promotes T-cell memory via transcriptional FOXO1-TCF1-Eomes programs and AMPKα1-ULK1-ATG7 metabolic axis, and that AMPKα1 plays a critical role in RIM-induced T-cell memory.


2021 ◽  
Author(s):  
Gaia Montacchiesi ◽  
Luigia Pace

2021 ◽  
Author(s):  
Colleen M. Lau ◽  
Gabriela M. Wiedemann ◽  
Joseph C. Sun

2021 ◽  
pp. ji2100452
Author(s):  
Aizhang Xu ◽  
Scot C. Leary ◽  
Md. Fahmid Islam ◽  
Zhaojia Wu ◽  
Kalpana Kalyanasundaram Bhanumathy ◽  
...  
Keyword(s):  
T Cell ◽  

2021 ◽  
Author(s):  
Saleh Abdel-Hafeez ◽  
Sanabel Otoom ◽  
Muhannad Quwaider

Memory Alias Table exploits a major role in Register Renaming Unit (RRU) for maintaining the translation between logical registers to physical registers for the given instruction(s). This work presents the design of the memory Alias Table based on the 8TCell with multiport write, read, and content-addressable operation for 2-WAY three operands machine cycle. Results show that four read ports operate simultaneously within a half-cycle, while two-write ports operate simultaneously within the other half-cycle. The operation of content-addressable with two parallel ports is managed during the half-cycle of the read phase; thus, the three operations occur within a single cycle without latency. HSPICE simulations conduct 32-rows x 6-bit with 21T-Cell memory Alias Table that has 4- read ports, 2-write ports, and 2-content-addressable ports using a standard 65 nm/1V CMOS process. Simulations reveal that the proposed design operates within a one-cycle of 1 GHz consuming an average power of 0.87 mW


2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Kaitlin A. Read ◽  
Kenneth J. Oestreich

For over a decade, mutual antagonism between the transcriptional repressors Bcl-6 and Blimp-1 has been appreciated as a key mechanistic determinant of lymphoid differentiation programs. Now, in this issue of JEM, Ciucci et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202343) demonstrate that this relationship is "central" to the generation of T cell memory.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2794-2794
Author(s):  
Lior Goldberg ◽  
Eric R Haas ◽  
Vibhuti Vyas ◽  
Ryan Urak ◽  
Stephen J Forman ◽  
...  

Abstract T cell adaptive immune response requires cellular plasticity to generate distinct subsets with diverse functional and migratory capacities. By expressing unique patterns of trafficking molecules, T cells interact with tissue-specific vascular endothelia for preferential recruitment to distinct tissues. Chimeric antigen receptors (CARs) are synthetically engineered receptors that redirect the specificity, effector function, and metabolism of transduced T cells. Studies of CAR T cells have primarily focused on a limited number of phenotypic markers in blood, representing an incomplete view of CAR T cell complexity. To address this need, we used cytometry by time of flight (CyTOF) which enables high dimensional, in-depth, proteomic analysis of immune cells at the single-cell level. We designed an integrative panel with antibodies specific for CAR, cell lineage, activation, maturation, trafficking, and exhaustion markers (Figure 1A), and investigated the spatiotemporal landscape of CD19 CAR T cells across patients' tissues. To interrogate the spatiotemporal dynamics of CAR T cells in vivo we analyzed clinical samples from three patients treated with CD19 CAR T cells for B cell hematological malignancies. For each patient we sampled the leukapheresis T cells, CAR product, PMBCs on days 7 and 28, BM on day 28 and cerebrospinal fluid on day 7 or 28 post CAR T cell infusion (Figure 1B). Patients CAR product revealed upregulation in most of the trafficking and activation molecules compared to leukapheresis T cells as baseline. Remarkably, the human tissue samples showed diverse spatiotemporal landscapes. For example, CSF samples were enriched in activation markers such as CD25, CD27, CD95, granzyme B; trafficking proteins such as integrin β7, CD11a, CD49d, CD62L, CD69, CCR7, CXCR3, CXCR4 and had diminished exhaustion marker PD-1 (Figure 1C). To further explore the spatiotemporal dynamics, we employed FlowSOM which identified 21 distinct clusters (Figure 1D). Quantitation of clusters frequency and protein expression revealed significant heterogeneity, individual clusters showed different patterns of expansion and contraction by time and place (Figure 1E). For example, leukapheresis T cells were solely enriched in clusters 1-2 marked by CD45RA CD27, and CCR7 expression, while CAR product was enriched in clusters 9,11, and 13 marked by CXCR3, integrin β7 trafficking molecules and granzyme B expression. Furthermore, day 7 peripheral blood samples were solely enriched in clusters 19-20 marked by the expression of the activation markers HLA-DR, CD25, and granzyme B, in addition to the trafficking proteins CD49d, CD62L and CXCR3. Notably, cluster 12 which had low abundance in the leukapheresis T cells and was depleted in the CAR product, dominated day 7 peripheral blood samples, and persisted to a lesser degree in all tissue samples. Moreover, clusters 3 and 4 that were enriched in the CSF expressed high CXCR3, CXCR4, CCR7, integrin β7, CD62L, and CD49b which may attribute to their migration between blood and CSF. Since CAR T cells are genetically modified T cells with distinct properties, we next asked to evaluate the phenotypic similarities between patients' tissue CAR T cells and T cell subsets in healthy donor PBMCs. Spearman correlation analysis demonstrated strong positive correlation between leukapheresed T cells and Naïve/stem cell memory phenotypes. Whereas, peripheral blood samples correlated the most with effector and effector memory phenotype, notably on day 28 post infusion. Interestingly, CSF samples possessed features of central/stem cell memory phenotype, mirroring our preclinical findings where CAR T cells exposed into CSF are memory-like T cells. (Wang, et al, Cancer Immunol Res, 2021), and BM CAR T cells, correlated with both effector and memory phenotypes, highlighting the role of the BM as a T cell memory niche. In summary, mass cytometry enabled us for the first time, to our knowledge, to provide insights into the spatiotemporal plasticity of CAR T cell therapy. We revealed remarkable diversification within patients CAR T cells and their spatiotemporal relationship to T cells specialization within the human immune system and identified tissue specific CAR T cell expression profiles. Our work provides a potential framework to remodel CAR T cells for enhanced immunotherapy efficacy. Figure 1 Figure 1. Disclosures Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy. Wang: Pepromene Bio, Inc.: Consultancy.


Author(s):  
Rūta Veinalde ◽  
Gemma Pidelaserra-Martí ◽  
Coline Moulin ◽  
Lara M. Jeworowski ◽  
Linda Küther ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document