| First Author | Xie J | Year | 2019 |
| Journal | J Leukoc Biol | Volume | 105 |
| Issue | 3 | Pages | 565-575 |
| PubMed ID | 30624806 | Mgi Jnum | J:295132 |
| Mgi Id | MGI:6459674 | Doi | 10.1002/JLB.4A0718-292R |
| Citation | Xie J, et al. (2019) Sepsis erodes CD8(+) memory T cell-protective immunity against an EBV homolog in a 2B4-dependent manner. J Leukoc Biol 105(3):565-575 |
| abstractText | Epstein-Barr virus (EBV) reactivation commonly occurs following sepsis, but the mechanisms underlying this are unknown. We utilized a murine EBV homolog (gHV) and the cecal ligation and puncture model of polymicrobial sepsis to study the impact of sepsis on gHV reactivation and CD8(+) T cell immune surveillance following a septic insult. We observed a significant increase in the frequency of gHV-infected germinal center B cells on day 7 following sepsis. This increase in viral load was associated with a concomitant significant decrease in the frequencies of gHV-specific CD8(+) T cells, as measured by class I MHC tetramers corresponding to the immunodominant viral epitopes. Phenotypic analysis revealed an increased frequency of gHV-specific CD8(+) T cells expressing the 2B4 coinhibitory receptor in septic animals compared with sham controls. We sought to interrogate the role of 2B4 in modulating the gHV-specific CD8(+) T cell response during sepsis. Results indicated that in the absence of 2B4, gHV-specific CD8(+) T cell populations were maintained during sepsis, and gHV viral load was unchanged in 2B4(-/-) septic animals relative to 2B4(-/-) sham controls. WT CD8(+) T cells upregulated PD-1 during sepsis, whereas 2B4(-/-) CD8(+) T cells did not. Finally, adoptive transfer studies revealed a T cell-intrinsic effect of 2B4 coinhibition on virus-specific CD8(+) T cells and gHV viral load during sepsis. These data demonstrate that sepsis-induced immune dysregulation erodes antigen-specific CD8(+) responses against a latent viral infection and suggest that blockade of 2B4 may better maintain protective immunity against EBV in the context of sepsis. |
