Role of CD8⁺ T cells versus CD8α⁺ DCs in HSV-1 latency-reactivation

Abstract

Purpose : To evaluate whether CD8⁺ T cells play a bystander or functional role during the course of latency-reactivation in trigeminal ganglia (TG) of latently infected mice.

Methods : Wild-type, CD8α^-/- (lack functional CD8⁺ T cells and CD8α⁺ DCs), CD8β^-/- (have functional CD8α⁺ T cells and CD8α⁺ DCs), β2m^-/- (lack functional CD8⁺ T cells but have CD8α⁺ DCs), BXH2 (have functional CD8⁺ T cells but lack CD8α⁺ DCs), and CD4^-/- (have functional CD8⁺ T cells and CD8α⁺ DCs) mice were ocularly infected with virulent (McKrae) or avirulent (KOS) strains of HSV-1. Level of viral gB DNA and LAT RNA in TG on day 28 PI and virus reactivation on day 28 PI were measured. Some of mice received adaptive transfers of BM-derived CD8α⁺ DCs or CD8⁺ T cells before ocular infection.

Results : In these studies we have shown that TG from CD8α^-/- mice had a significantly lower level of latency and ex-plant reactivation than WT, β₂m^-/-, CD8β^-/- or CD4^-/- mice. Adoptive transfer of BM-derived CD8α⁺ DCs significantly increased the levels of latency in CD8α^-/- mice, while transfer of CD8⁺ T cells had no effect. Similarly BXH2 mice had a lower level of latency-reactivation than their control mice. Finally, LAT expression and increased latency correlated with an increased level of PD-1.

Conclusions : Our results suggested that: (1) higher latency and subclinical reactivation correlated with the presence of more CD8⁺ T cells expressing the PD-1 exhaustion marker; (2) CD8⁺ T cells were not responsible for increase or maintenance of latency in ocularly infected mice and this was independent of their higher exhaustion phenotype or strain of virus; and (3) CD8α⁺ DCs directly or as a critical helper for other cell types, contributed to higher latency-reactivation and thus exhaustion in TG of latently infected mice independent of CD8⁺ T cells.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.