The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis

Background: previous work from our laboratory has demonstrated that during acute viral brain infection,glial cells modulate antiviral t cell effector responses through the pd-1: pd-l1 pathway,thereby limiting the deleterious consequences of unrestrained neuroinflammation. here,we evaluated the pd-1: pd-l1 pathway in development of brain-resident memory t cells (btrm) following murine cytomegalovirus (mcmv) infection. methods: flow cytometric analysis of immune cells was performed at 7,14,and 30 days post-infection (dpi) to assess the shift of brain-infiltrating cd8+ t cell populations from short-lived effector cells (slec) to memory precursor effector cells (mpec),as well as generation of btrms. results: in wild-type (wt) animals,we observed a switch in the phenotype of brain-infiltrating cd8+ t cell populations from klrg1+ cd127- (slec) to klrg1- cd127+ (mpec) during transition from acute through chronic phases of infection. at 14 and 30 dpi,the majority of cd8+ t cells expressed cd127,a marker of memory cells. in contrast,fewer cd8+ t cells expressed cd127 within brains of infected,pd-l1 knockout (ko) animals. notably,in wt mice,a large population of cd8+ t cells was phenotyped as cd103+ cd69+,markers of btrm,and differences were observed in the numbers of these cells when compared to pd-l1 kos. immunohistochemical studies revealed that brain-resident cd103+ btrm cells were localized to the parenchyma. higher frequencies of cxcr3 were also observed among wt animals in contrast to pd-l1 kos. conclusions: taken together,our results indicate that btrms are present within the cns following viral infection and the pd-1: pd-l1 pathway plays a role in the generation of this brain-resident population. © 2017 the author(s).