Project description:Gene expression analysis of WT and IL-2Ra-deficient CTL (P14) isolated 8 days after inffection with LCMV. The goals of the study are to assess the impact of IL-2 signals on effector and memory CTL differentiation.
Project description:Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as “damage-associated molecular patterns” or “alarmins”, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses. 2 groups (wt vs. ST-/- P14 cells), 3 replicates per group.
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
Project description:Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to control the differentiation of effector CD8+ cytotoxic T cells (CTL). Using high-resolution mass spectrometry, we have generated an in-depth characterisation of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2-JAK1/3 signaling selectively regulated the abundance of a key subset of proteins influencing the accumulation of critical cytokines and effector molecules in T cells. Moreover, IL-2 controlled the concentration of proteins that support core metabolic processes essential for cellular fitness. One fundamental insight was the dominant role for IL-2 in controlling how effector T cells respond to their microenvironment. IL-2-JAK1/3 signaling pathways thus controlled the abundance of nutrient transporters, nutrient sensors and critical oxygen sensing molecules. The data provide key insights of how IL-2 controls T cell function and highlight signaling mechanisms and transcription factors that link oxygen sensing to transcriptional control of CD8+ T cell differentiation.
