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Series GSE35547 Query DataSets for GSE35547
Status Public on Feb 04, 2012
Title Notch controls the magnitude of CD4+ T cell responses by promoting cellular longevity
Organism Mus musculus
Experiment type Expression profiling by array
Summary Generation of effective immune responses requires expansion of rare antigen-specific CD4+ T cells. The magnitude of the response is ultimately determined by proliferation and survival. Both processes are tightly controlled to limit responses to innocuous antigens. Sustained expansion occurs only when innate immune sensors are activated by microbial stimuli or by adjuvants, which has important implications for vaccination. The molecular identity of the signals controlling sustained T cell responses is not fully clear. Here we describe a prominent role for the Notch pathway in this process. Co-activation of Notch allows accumulation of far greater numbers of activated CD4+ T cells than stimulation via T cell receptor and classical co-stimulation alone. Notch does not overtly affect cell cycle entry or progression of CD4+ T cells. Instead, Notch protects activated CD4+ T cells against apoptosis after an initial phase of clonal expansion. Notch induces a broad anti-apoptotic gene expression program, which protects against intrinsic as well as extrinsic apoptosis pathways. Both Notch1 and Notch2 receptors and the canonical effector RBPJ are involved in this process. Correspondingly, CD4+ T cell responses to immunization with protein antigen are strongly reduced in mice lacking these components of the Notch pathway. Our findings therefore show that Notch controls the magnitude of CD4+ T cell responses by promoting cellular longevity.
 
Overall design Naïve CD4+ T cells were activated for 1 day (1 control sample and 1 experimental sample) or 3 days (3 control samples and 3 experimental samples) with antibodies to CD3 soluble and CD28 in the presence of recombinant Delta4-Ig (experimental samples) or control Ig (control samples).
 
Contributor(s) Helbig C, Moerland PD, Amsen D
Citation(s) 22615412
Submission date Feb 03, 2012
Last update date Jun 14, 2018
Contact name Derk Amsen
E-mail(s) D.Amsen@amc.nl
Phone 0031205664977
Organization name AMC
Street address Meibergdreef 9
City Amsterdam
ZIP/Postal code 1105AZ
Country Netherlands
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (8)
GSM870390 C-Ig day1_mouse1
GSM870391 C-Ig_day3_mouse1
GSM870392 DLL4_day1_mouse1
Relations
BioProject PRJNA152281

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE35547_RAW.tar 3.1 Mb (http)(custom) TAR
GSE35547_non-normalized.txt.gz 1.3 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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