Department of Pathology; Immunology and Virology Program
Cells | Immunology of Infectious Disease | Immunopathology | Pathogenic Microbiology | Viruses
Virus infections are known to induce a transient state of immune suppression often associated with an inhibition of T cell proliferation in response to mitogen or cognate-antigen stimulation. Recently, virus-induced immune suppression has been linked to responses to type 1 interferon (IFN), a signal 3 cytokine that normally can augment the proliferation and differentiation of T cells exposed to antigen (signal 1) and co-stimulation (signal 2). However, pre-exposure of CD8 T cells to IFN-inducers such as viruses or poly(IratioC) prior to antigen signaling is inhibitory, indicating that the timing of IFN exposure is of essence. We show here that CD8 T cells pretreated with poly(IratioC) down-regulated the IFN receptor, up-regulated suppressor of cytokine signaling 1 (SOCS1), and were refractory to IFNbeta-induced signal transducers and activators of transcription (STAT) phosphorylation. When exposed to a viral infection, these CD8 T cells behaved more like 2-signal than 3-signal T cells, showing defects in short lived effector cell differentiation, reduced effector function, delayed cell division, and reduced levels of survival proteins. This suggests that IFN-pretreated CD8 T cells are unable to receive the positive effects that type 1 IFN provides as a signal 3 cytokine when delivered later in the signaling process. This desensitization mechanism may partially explain why vaccines function poorly in virus-infected individuals.
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DOI of Published Version
PLoS Pathog. 2014 Sep 25;10(9):e1004357. doi: 10.1371/journal.ppat.1004357. eCollection 2014. Link to article on publisher's site
Urban, Stina L. and Welsh, Raymond M., "Out-of-sequence signal 3 as a mechanism for virus-induced immune suppression of CD8 T cell responses" (2014). Open Access Articles. 2461.
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This work is licensed under a Creative Commons Attribution 4.0 License.