Cutting Edge: CD8 T Cells Specific for Lymphocytic Choriomeningitis Virus Require Type I IFN Receptor for Clonal Expansion

Abstract

The role of type I IFN signaling in CD8 T cells was analyzed in an adoptive transfer model using P14 TCR transgenic CD8 T cells specific for lymphocytic choriomeningitis virus (LCMV) but deficient in type I IFNR. In the present study, we demonstrate severe impairment in the capacity of P14 T cells lacking type I IFNR to expand in normal type I IFNR wild-type C57BL/6 hosts after LCMV infection. In contrast, following infection of recipient mice with recombinant vaccinia virus expressing LCMV glycoprotein, P14 T cell expansion was considerably less dependent on type I IFNR expression. Lack of type I IFNR expression by P14 T cells did not affect cell division after LCMV infection but interfered with clonal expansion. Thus, direct type I IFN signaling is essential for CD8 T cell survival in certain viral infections.

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

“…Using adoptive transfer of CD8 1 P14 T cells, Kolumam et al demonstrated that functional IFNAR signaling was essential for sustaining T-cell memory upon LCMV infection [23]. In a collaborative study, we also observed enhanced expansion of adoptively transferred CD8 1 P14 T cells upon LCMV infection, whereas upon VACV infection this effect was less pronounced [12]. The critical issue of differentially induced IFN, depending on the used pathogen, was further addressed by Thompson et al by stimulating transferred CD8 1 P14 or CD8 1 OT-I T cells with LCMV or recombinant OVAexpressing VACV, vesicular stomatitis virus, and Listeria monocytogenes [31].…”

“…Previously, it was shown that upon LCMV infection expansion of gp33-specific T cells was dependent on IFNAR-triggering of T cells, whereas after VACV gp33 infection expansion of specific T cells was less IFNAR-dependent [12]. To further elaborate on this observation, in a first step we performed adoptive transfer experiments.…”

“…The critical issue of differentially induced IFN, depending on the used pathogen, was further addressed by Thompson et al by stimulating transferred CD8 1 P14 or CD8 1 OT-I T cells with LCMV or recombinant OVAexpressing VACV, vesicular stomatitis virus, and Listeria monocytogenes [31]. In line with Aichele et al [12] Thompson et al found that in contrast to LCMV infection with VACV, vesicular stomatitis virus, or Listeria induced only partially IFNAR-dependent CD8 1 T-cell expansion. Similarly, upon infection with murine Sendai virus IFN unresponsive mice developed long-term immunity including protective CD8 1 T cells and antibodies [32].…”

“…In one report, lack of direct IFNAR-signaling on the level of CD8 1 T cells was associated with reduced expansion of gp33-specific T cells upon infection with lymphocytic choriomeningitis virus (LCMV). This phenomenon was less pronounced upon infection with VACV gp33 [12]. Interestingly, instead of enhancing T-cell function, IFN can also lead to T-cell attrition or activation induced cell death [13,14].…”

“…Nevertheless, little is known about cellular and viral mechanisms that are associated with high immunogenicity of MVA. Considering the ability of MVA to induce IFN responses in the serum, whereas VACV does not [16], these two closely related virus strains are an ideal model to study the impact of virus-induced IFN on adaptive immunity.Previously, it was shown that upon LCMV infection expansion of gp33-specific T cells was dependent on IFNAR-triggering of T cells, whereas after VACV gp33 infection expansion of specific T cells was less IFNAR-dependent [12]. To further elaborate on this observation, in a first step we performed adoptive transfer experiments.…”