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| Status |
Public on Dec 31, 2015 |
| Title |
Modulation of T cell responses by type I interferons |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Type I interferons (IFNs) play a key role in linking the innate and adaptive immune responses. IFNs can have both positive and negative effects on the development of memory CD8+ T cells, but their contribution to the priming of naïve T cells is unclear. Using OT-I TCR transgenic T cells, we show strong effects on TCR-induced functional response when sensitized by IFN-β prior to their stimulation with cognate antigen. These effects are only seen in the absence of co-stimulation and at suboptimal TCR stimulation conditions. Pre-stimulation of naïve T cells inhibits certain TCR-mediated functions like cell proliferation and the induction of genes such as IFN-γ and IL-2. However, type I IFN does not influence the induction of other TCR-induced functions like the expression of the T cell activation marker CD25 and a number of other genes. IFN-mediated impairment of proliferation is due to the lack of IL-2 induction since it can be compensated by exogenous IL-2. Further analysis reveals an IFN-mediated inhibition of Ca2+ flux and ERK phosphorylation. In vivo studies confirm that pre-stimulation with IFNs inhibits early T cell responses, whereas long-term responses are positively affected. Our results reveal that IFN exerts negative effects on naïve T cells in a timely defined range under sub-optimal TCR stimulation conditions. These results highlight the importance of timing of immune-regulatory events and reveal a novel role for type I IFNs by shaping the immune response, such that T cells are not able to react until optimal stimulation is provided.
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| Overall design |
8 Arrays, untreated cells as references, IFNb treatment and/or TCR stimulation at various lengths of time
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| |
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| Contributor(s) |
Kröger A, Neumann B, Hauser H, Dietrich-Breitholtz O |
| Citation missing |
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| Submission date |
Oct 05, 2012 |
| Last update date |
May 10, 2018 |
| Contact name |
Andrea Kröger |
| E-mail(s) |
andrea.kroeger@helmholtz-hzi.de
|
| Phone |
+49 531 6181 5060
|
| Fax |
+49 531 6181 5002
|
| Organization name |
Helmholtz Centre for Infection Research
|
| Department |
Regulation and Differentiation
|
| Street address |
Inhoffenstrasse 7
|
| City |
Braunschweig |
| ZIP/Postal code |
38124 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
|
| Samples (8)
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| Relations |
| BioProject |
PRJNA176720 |
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