Abstract
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(I∶C) 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(I∶C) down-regulated the IFN receptor, up-regulated suppressor of cytokine signaling 1 (SOCS1), and were refractory to IFNβ-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.
Highlights
The fact that virus infections can induce a transient state of immune suppression was first described over a century ago, as patients acutely infected with the measles virus failed to develop a recall response to tuberculin even though they had previously been immunized [1]
The efficacy of vaccines can be affected by a number of different factors. It has been known for some time that suppression of the immune system occurs during acute viral infections
We have identified a common mechanism of immune suppression that may occur with many different pathogens that induce a particular inflammatory response
Summary
The fact that virus infections can induce a transient state of immune suppression was first described over a century ago, as patients acutely infected with the measles virus failed to develop a recall response to tuberculin even though they had previously been immunized [1]. Virus-induced immune suppression can affect many aspects of the immune system, it is often associated with a reduced ability of T cells to proliferate in response to mitogens or antigen-specific stimulation. Viruses may induce this suppression by directly infecting cells of the immune system, but they can induce immune suppression without directly targeting hematopoietic cells. Recent in vivo studies from our laboratory showed that type 1 IFN can be a profound and universal factor inducing suppression of T cell proliferation during viral infections if the T cells are exposed to type 1 IFN prior to encountering their cognate ligand [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
