Neonatal naïve CD8+ T cells have effector-like gene expression that prevents memory cell formation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Andrew Grimson
PROVIDER: E-GEOD-65923 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Neonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, naïve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in naïve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal naïve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. total RNAs were sequenced from adult and neonatal CD8+ T cells before and during infection
2015-09-24 | E-GEOD-65922 | biostudies-arrayexpress
Project description:Neonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, naïve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in naïve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal naïve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. PolyA RNA was selected and sequenced from adult and neonatal CD8+ T cells before and during infection
2015-09-24 | E-GEOD-65921 | biostudies-arrayexpress
Project description:Neonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, naïve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in naïve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal naïve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Small RNAs were sequenced from adult and neonatal CD8+ T cells before and during infection
2015-09-24 | E-GEOD-65920 | biostudies-arrayexpress
Project description:Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. Here we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. While adult CD8+ T cells differentiated into a heterogeneous pool of effector and memory cells, neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and exhibited a distinct gene expression profile. Surprisingly, impaired neonatal memory formation was not due to a lack of responsiveness, but instead because neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became terminally differentiated. Collectively, these findings demonstrate that neonatal CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell differentiation, which impairs the formation of memory CD8+ T cells in early life mRNA profiles of effector CD8+ T cells from neonatal and adult mice
2014-05-13 | E-GEOD-56575 | biostudies-arrayexpress
Project description:TCF-1 is an HMG family transcription factor which is known to be activated by the canonical Wnt signaling pathway and modulated by other signals such as those derived from T cell receptor. We found that during CD8 T cell responses, TCF-1 deficiency impaired long-term maintenance of antigen-specific memory CD8 T cells. We used microarrays to detect gene expression changes in memory CD8 T cells caused by TCF-1 deficiency. Host mice that received WT or TCF-1-deficient OT-I CD8 T cells were infected with attenuated Listeria monocytogenes expressing Ova peptide. In memory phase (i.e., more than 80 days post infection), antigen-specific T cells were ioslated by cell sorting. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).
2010-10-04 | E-GEOD-20754 | biostudies-arrayexpress
Project description:Gene expression analysis of tumor-specific CD8 T cells encountering a tumor-specific antigen in pre-malignant lesions in the liver at different time points post tumor initiation. The overall goal of this mouse study was to elucidate the molecular program in tumor-specific T cells encountering a tumor-specific antigen in pre-malignant lesions. The study identifies the genes and pathways that are dysregulated in tumor-specific T cells associated with T cell unresponsiveness in tumors. To identify the genes and pathways that are dysregulated in tumor-specific T cells. Gene signatures of the following sample groups were compared: 1. Naïve CD8 T cells; 2. Effector CD8 T cells; 3. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 8-12 days after tumor induction. 4. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 32-34 days after tumor initiation. The mouse tumor model that was used is an autochthonous, tamoxifen-inducible liver cancer model (ASTxCre-ERT2; AST=Albumin-floxStop-SV40 large T antigen; Cre-ERT2 = TAM-dependent Cre-recombinase) in which the SV40 large T antigen serves as the oncogenic driver and tumor-specific antigen; SV40-I TCR transgenic mice, whose CD8 T cells express a Db-restricted TCR specific for the Tag epitope I were used as source of naïve tumor-specific CD8 T cells (TCRSV40-I) Total RNA was isolated from flow-sorted transgenic CD8 TCRSV40-I T cells from the following sample groups: Naïve, effector, D8-12-pre-malignant lesions, and D32-34 pre-malignant lesions.
2016-08-11 | E-GEOD-60501 | biostudies-arrayexpress
Project description:microRNA-150 (miR-150) is mainly expressed in the lymph nodes and spleen and is highly up-regulated during the development of mature T and B cells. To understand the signal-transduction network for 'effector or memory T cells' and 'mir-150' in naM-CM-/ve, effector, or memory CD8 T cells of mir-150 knockout and wild-type mice, we analyzed gene expression profiles by microarray. The genetic background of the cells used in this study is CD8 T cells from spleen of the 8 week-old male C57BL/6J mice (for female: WT-memory_2 & KO-memory_2). Corresponding authors: Inpyo Choi, PhD, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro,Yuseong, Daejeon 305-806, Republic of Korea. E-mail: ipchoi@kribb.re.kr. Or: Tae-Don Kim, PhD, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong, Daejeon 305-806, Republic of Korea. E-mail: tdkim@kribb.re.kr. wild-type[WT] vs. mir-150 knockout[KO]; naM-CM-/ve, effector, and memory CD8 T cells.
2014-10-11 | E-GEOD-62262 | biostudies-arrayexpress
Project description:Expression profiling by microarray was used with a murine listeriosis model to better understand increased susceptibility of preterm neonates to infection. We used DNA microarray to identify genes that were differentially expressed in liver of adult and neonatal Balb/c mice after listeriosis infection. A murine listeriosis model was established. The methods for culturing and counting the Listeria monocytogenes (strain CNL 85/163) had been described in previous publications. The Listeria was injected intraperitoneally using a 1-mL U-100 insulin syringe with a 30 gauge needle. Doses of Listeria monocytogenes used were based on work by our laboratory showing that similar bacterial colony counts were obtained with 4.2 x 10^5 total Listeria per adult mouse and 150 Listeria per gram for 3 to 5 day old neonatal mice. In neonatal mice, great care was taken to void deep intraperitoneal injection towards the viscera, or across the central abdominal vessels. At specified time points, liver was removed upon animal sacrifice and immediately flash frozen in liquid nitrogen and stored at -80 degrees Centigrade. Three adult mice and three neonatal mice were used at each time point.
2013-06-01 | E-GEOD-45051 | biostudies-arrayexpress
Project description:A time course of OTI CD8 T cells transferred to irradiated syngeneic hosts (or unirradiated hosts as control).
2007-11-02 | E-GEOD-1921 | biostudies-arrayexpress
Project description:Differentiation of CD8+ T lymphocytes into effector and memory cells is key for an adequate immune response and relies on complex interplay of pathways that convey signals from cell surface to nucleus. In this study, we fractionated four CD8+ T cell subtypes; naïve, recently activated effector, effector and memory cells into membrane, cytosol, soluble nucleus, chromatin-bound and cytoskeleton compartments. Using LC-MS/MS analysis, identified peptides were matched to human peptides/proteins (SwissProt). Compartment fractionation and gel-LC-MS separation identified 2399 proteins in total. Among these 735 were detected in all five, 241 in four, 257 in three, 368 in two and 798 found in only one fraction. Comparison between the two most different subsets, naïve and effector, yielded 146 significantly regulated proteins.
2015-02-04 | PXD001065 | Pride