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GSE10239
Mus musculus
12 Downloadable Samples
Description
Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation
Publication Title
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
CD25, the high affinity interleukin-2 (IL-2) receptor alpha-chain, is rapidly upregulated by antigen-specific CD8+ T cells after T cell receptor stimulation. We demonstrated that during an acute viral infection, CD25 expression was dynamic, and a subset of virus-specific CD8+ T cells sustained CD25 expression longer than the rest. Examination of the in vivo fate of effector CD8+ T cells exhibiting differential responsiveness to IL-2 revealed that CD25lo cells, which were relatively less sensitive to IL-2, preferentially upregulated CD127 and CD62L and gave rise to the functional long-lived memory pool. In contrast, CD25hi cells that accumulate enhanced IL-2 signals, proliferated more rapidly, were prone to apoptosis, exhibited a more pronounced effector phenotype, and appeared to be terminally differentiated. Sustained IL-2 receptor signaling resulted in increased CD8+ T cell proliferation, higher granzyme B expression and exaggerated contraction after antigen clearance. These data support the hypothesis that prolonged IL-2 signals during priming promote terminal effector differentiation of CD8+ T cells.
Publication Title
Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection.
Publication Title
PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
The objective of this study was to identify alterations in gene expression during reverse myocardial remodeling in a mouse model of reversible pressure overload.
Publication Title
Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Understanding the response of memory CD8 T cells to persistent antigen re-stimulation and the role of CD4 T cell help is critical to the design of successful vaccines for chronic diseases. However, studies comparing the protective abilities and qualities of memory and nave cells have been mostly performed in acute infections, and little is known about their roles during chronic infections. Herein, we show that memory cells dominate over nave cells and are protective when present in large enough numbers to quickly reduce infection. In contrast, when infection is not rapidly reduced, memory cells are quickly lost, unlike nave cells. This loss of memory cells is due to (i) an early block in cell proliferation, (ii) selective regulation by the inhibitory receptor 2B4, and (iii) increased reliance on CD4 T cell help. These findings have important implications towards the design of T cell vaccines against chronic infections and tumors.
Publication Title
Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load.
Sample Metadata Fields
Specimen part
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