The timing of IFN exposure can greatly affect the T-cell differentiation pathway and the magnitude of the T-cell response. It is well established that exposure to IFNγ promotes the differentiation of CD4 T cells into IFNγ-secreting Th1 cells 
, but here we are talking about a timing-dependent exposure of CD8 T cells to type 1 IFN. Exposure of naïve CD8 T cells to APC and IFN before exposure to cognate antigen upregulates the T-cell expression of eomesodermin and sensitizes T cells to enter an altered differentiation pathway on encounter with cognate antigen () 
. Instead of undergoing several divisions before exerting effector functions, these sensitized CD8 T cells retain a naïve antigenic phenotype but act like memory cells and develop effector-cell properties associated with cytokine production and cytolytic activity within 2–4 h. This is not due to a direct effect of IFN on the T cells, as it occurs even if T cells lack IFN1R. It is more likely due to IFN acting on the APCs, which need to express the restricting MHC molecule for the cognate peptide to sensitize the T cells to respond differently to the cognate peptide.
We propose that the enhanced expression of MHC- presenting self-peptide provides a low level stimulus to naïve T cells, enabling them to retain a naïve T-cell antigenic phenotype yet produce transcription factors that allow them to respond to cognate peptide like a memory T cell.
A common phenomenon occurring during the course of a viral infection is a transient immune deficiency whereby T cells respond poorly to T-cell mitogens in vitro and to challenge with nonviral antigens in vivo 
; this is, in fact, why one should not get vaccinated during illness. Several phenomena could account for this deficiency, including growth of virus in T cells, impaired antigen presentation, competition for T-cell growth factors, and induction of activation-induced cell death in a Fas ligand-rich environment. However, we have recently shown that type 1 IFN itself may account for much of this immune suppression, if the T cells are exposed to the IFN before cognate antigen encounter () 
. Prior exposure to IFN before cognate antigen stimulus impairs the proliferation of T cells after the antigen stimulus, even in the presence of IFN acting as a costimulatory factor, and the inhibition of proliferation in this case requires IFN1R on the T cells. The molecular mechanism for this IFN-induced impairment of proliferation is unknown, but this is reminiscent of earlier work showing that NK cells become hyporesponsive to IFN-mediated activation after having received a prior IFN stimulus 
Therefore, T cells that receive an IFN stimulus prior to cognate antigen exposure become sensitized to immediately become effector cells by an indirect IFN-dependent mechanism; but they undergo reduced proliferation by a direct IFN-dependent mechanism. Together these mechanisms may limit de novo T-cell responses in the midst of a viral infection and may aid in the synchronization of the contraction phase of the immune response, because T cells recruited late into the antiviral response would undergo reduced clonal expansion.