Type 1 interferons (IFNs) were the first cytokines discovered and include IFNb,. ten forms of IFNa, and several other related molecules that all bind to the same type 1 IFN receptor (IFN1R). Type 1 IFNs are commonly referred to as ‘‘viral’’IFNs because they can be induced directly by virus infections, in contrast to ‘‘immune’’IFN, or IFNc, which is synthesized after receptor engagement of T cells and natural killer (NK) cells during immune responses. Type 1 IFNs get induced by viral nucleic acids and proteins acting on cellular signaling molecules such as Tolllike receptors and RNA helicases, which, in turn, release transcription factors into the nucleus. Mice lacking IFN1R appear normal in a pathogen-free environment but are extraordinarily susceptible to virus infections [1]. This susceptibility is partially due to IFN-regulated genes that suppress viral replication, but type 1 IFNs also have many immunoregulatory properties that could also affect host susceptibility to infection.

Indications of the immunoregulatory roles of type 1 IFN came in the 1970s with observations that IFN upregulated the expression of class 1 MHC antigens [2], enhanced histamine secretion by triggered Mast cells [3], and cytolytically activated NK cells [4–6]. Several studies showed that addition of IFN to mixed lymphocyte cultures could enhance or inhibit T-cell proliferation, depending on the dose [7]. IFN was then shown to elicit NK cell proliferation in vivo by a mechanism involving the induction of IL-15, a growth factor for NK cells [8, 9]; a similar phenomenon of IFN and IL-15 was later shown for the division of memory T cells [10]. In the past decade a substantial number of new insights have developed in regards to how IFN can directly or indirectly affect T-cell responses to viral infections. IFN can affect T-cell responses by acting on the antigen-presenting cells (APCs), by acting on the T cells, or by inducing other cytokines and chemokines that regulate T-cell responses. Of note is that the phenotype of the T cells and the timing of IFN exposure are of essence, as IFN can inhibit proliferation or induce apoptosis under some circumstances yet be dramatically stimulatory under other conditions. Depending on their activation