Project description:Chronic viral infection disrupts memory B cell development. We used single cell ATAC sequencing (scATAC-seq) to analyze chromatin accessibility in antigen-specific B cells responding to acute versus chronic LCMV infection.
Project description:Chronic viral infection disrupts memory B cell development. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of antigen-specific B cells responding to acute versus chronic LCMV infection.
Project description:Chromatin accessibility profile at the single cell level of splenic LCMV-specific B cells in acute versus chronic LCMV infection [scATAC-seq]
Project description:Chromatin accessibility profile of splenic LCMV-specific memory B cells following type I or II interferon blockade in acute versus chronic LCMV infection
Project description:Dynamics of interferon signalling impact the adaptive immune response. We used ATAC sequencing (ATAC-seq) to analyze chromatin accessibility in memory B cells from mice infected with acute or chronic LCMV infection, treated with type I or type II interferon blocking antibodies.
Project description:CD4 and CD8 T cells display functional defects during chronic infection such as loss of certain cytokines. Recent studies have suggested that CD4 T cells may actually gain other functions, however. Here, we analyzed gene expression profiles from LCMV-specific CD4 and CD8 T cells throughout the response to either acute LCMV or chronic LCMV infection. This alllowed us to identify CD4-specific changes during chronic infection compared to acute infection but also revealed shared core regulators between CD4 and CD8 T cells. LCMV-specific CD4 and CD8 T cells were isolated 6, 8, 15 and 30 days post infection with LCMV Armstrong or LCMV clone 13. Naïve CD4 and CD8 T cells were also isolated from naïve mice as comparisons. Four replicates of each sample were hybridized. The only exception is LCMV-specific CD4 T cells isolated 6 days post infection with LCMV-Arm where only three replicates were hybridized.
Project description:Gene expression profile at the single cell level of splenic LCMV-specific B cells in acute versus chronic LCMV infection [scRNA-seq, CITE-seq]
Project description:Understanding the response of memory CD8 T cells to persistent antigen re-stimulation and the role of CD4 T cell help is critical to the design of successful vaccines for chronic diseases. However, studies comparing the protective abilities and qualities of memory and naïve cells have been mostly performed in acute infections, and little is known about their roles during chronic infections. Herein, we show that memory cells dominate over naïve cells and are protective when present in large enough numbers to quickly reduce infection. In contrast, when infection is not rapidly reduced, memory cells are quickly lost, unlike naïve cells. This loss of memory cells is due to (i) an early block in cell proliferation, (ii) selective regulation by the inhibitory receptor 2B4, and (iii) increased reliance on CD4 T cell help. These findings have important implications towards the design of T cell vaccines against chronic infections and tumors. 16 samples are analyzed: 3 replicates of secondary effector CD8 P14 T cells at day 8 post-acute lymphocytic choriomeningitis virus (LCMV) infection; 4 replicates of secondary effector CD8 P14 T cells at day 8 post-chronic LCMV infection; 4 replicates of primary effector CD8 P14 T cells at day 8 post-acute LCMV infection; and 5 replicates of primary effector CD8 P14 T cells at day 8 post-chronic LCMV infection.
Project description:CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. Here we evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality following challenge with a persistent form of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. Splenic GP66-specific CD4 T cells from mice immunized with either a LMwt vaccine (sham) or LMgp61 vaccine (CD4 vaccine) were purified by FACS on day 8 post-infection with LCMV clone 13