Cytomegalovirus infection promotes the generation of IL-15-responsive CD57+ virtual memory CD8 T cells in people with and without HIV 2972

Abstract Description The CD8 T cell response is substantially dysregulated in people with HIV (PWH) on antiretroviral therapy (ART) compared to people without HIV (PWoH). Most PWH on ART harbor latent cytomegalovirus (CMV) infection, which is also associated with T cell perturbations, but what effects are driven by HIV versus CMV are currently unclear. Here we characterized eight CD8 T cell memory populations in PWoH and PWH, with or without CMV. HIV and CMV were each significantly associated with a reduced naïve T cell compartment, and HIV, but not CMV, was significantly associated with increased proportions of transitional and effector memory populations. CMV, on the other hand, was associated with a significant increase in virtual memory T cells (Tvm), a population with phenotypic and functional characteristics of memory cells, but that are thought to have not encountered their cognate antigens. Furthermore, CMV was significantly associated with increased expression of the senescence and cardiopathogenic marker CD57 on Tvm in both PWH and PWoH. CD57+ Tvm had reduced glucose uptake in response to T cell receptor engagement, but enhanced glucose uptake after IL-15 exposure, compared to CD57- Tvm. Neither total nor CD57+ Tvm were enriched for responses to CMV pp65 or HIV Gag peptides, consistent with the interpretation that ongoing interactions with homeostatic cytokines in CMV seropositive individuals drive accumulation of potentially immunopathogenic CD57+ Tvm in people with and without HIV. Funding Sources This work is supported by the Rustbelt Center for AIDS Research (AI036219) and National Institutes of Health grants AI162150 and AI167675 to MLF. Topic Categories Viral Immunology (VIR)