Project description:Regulatory T (Treg) cells act as terminators in the case of T cell immunity during the acute phase of viral infection. However, their roles in chronic viral infection are not completely understood. We compared the phenotype and function of Treg cells during acute and chronic viral infection using lymphocytic choriomeningitis virus-infected mouse models. Chronic infection, unlike acute infection, led to induction of Treg cells and upregulation of various inhibitory receptors. Treg cells isolated from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting T cell proliferation and subsequent cytokine production than those from naM-CM-/ve (naive Treg cells) or acutely infected mice (acute Treg cells). These gene expression profiles provided evidence that chronic Treg cells display characteristics distinct from either naive or acute Treg cells. Mouse splenic CD4+CD25+ regulatory T cells were analyzed at 0 day and 16 day after acute or chronic viral infection with LCMV Arm or CL13, respectively.
Project description:During acute viral infections, naïve CD4+ T cells differentiate into effector CD4+ T cells and, after viral control, into memory CD4+ T cells. Memory CD4+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD4+ T cells become less functional. To compare the development of functional memory T cells with poorly functional T cells from chronic viral infection, we generated longitudinal transcriptional profiles for each.
Project description:Trascriptional analysis of CD2 hi and CD25 lo CD4+ effector T cells during acute viral infection. SMARTA cells were transferred into B6 mice, followed by infection with LCMV. At day 5 post-infection, CD25 hi and CD25 lo SMARTA cells were isolated from the spleen by FACS. Consistent with our prior studies showing that CD25 lo early effector cells give rise to both Tfh effector cells and memory T cells, we observed gene expression in the CD25 lo population consistent with Tfh differentiation. Conversely, CD25 hi effector cells expressed markers consistent with Th1 differentiation and short-term survival.
Project description:During acute viral infections, naïve CD4+ T cells differentiate into effector CD4+ T cells and, after viral control, into memory CD4+ T cells. Memory CD4+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD4+ T cells become less functional. To compare the development of functional memory T cells with poorly functional T cells from chronic viral infection, we generated longitudinal transcriptional profiles for each. Naive CD44Lo CD4+ T cells were isolated and sorted from uninfected C57BL/6 mice and H2-IAb GP66-specific CD4+ T cells were sorted using MHC-II tetramers at d6, 8, 15, and 30 p.i. with either LCMV Arm or LCMV clone 13. RNA from these CD4+ T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays.
Project description:Regulatory T (Treg) cells act as terminators in the case of T cell immunity during the acute phase of viral infection. However, their roles in chronic viral infection are not completely understood. We compared the phenotype and function of Treg cells during acute and chronic viral infection using lymphocytic choriomeningitis virus-infected mouse models. Chronic infection, unlike acute infection, led to induction of Treg cells and upregulation of various inhibitory receptors. Treg cells isolated from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting T cell proliferation and subsequent cytokine production than those from naïve (naive Treg cells) or acutely infected mice (acute Treg cells). These gene expression profiles provided evidence that chronic Treg cells display characteristics distinct from either naive or acute Treg cells.
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.
Project description:The objective of the present study was to characterize the phenotype of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the course of parasitic Plasmodium yoelii (P .yoelii) infection of BALB/c mice. Therefore we performed microarray expression analysis of CD4+CD25+Foxp3+ Tregs isolated by FACS from spleens of non-infected mice and from spleens of mice infected with P. yoelii 3 days and 5 days post infection. By comparing the gene expression profiles, we were able to identify molecules which were differentially expressed by Tregs during parasitic infection and thereby might be involved in their immune-suppressive function. Moreover, we included CD4+CD25-Foxp3- T cells from spleens of non-infected and P. yoelii-infected mice in our analysis. It was proposed that immune-suppressive CD4+CD25-Foxp3- T cells might be induced during Plasmodium infection of mice. Thus, detailed gene expression data of these cells in comparison to CD4+CD25+Foxp3+ Tregs would contribute a better understanding in the phenotype. FACS sorted CD4+CD25+Foxp3+ Tregs and CD4+CD25-Foxp3- T cells from pooled spleens of non-infected Foxp3/ eGFP mice (served as reference) and from pooled spleens of P. yoelii infected Foxp3/ eGFP mice 3 days and 5 days post infection were analyzed as single probes.
Project description:The objective of the present study was to characterize the phenotype of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the course of parasitic Plasmodium yoelii (P .yoelii) infection of BALB/c mice. Therefore we performed microarray expression analysis of CD4+CD25+Foxp3+ Tregs isolated by FACS from spleens of non-infected mice and from spleens of mice infected with P. yoelii 3 days and 5 days post infection. By comparing the gene expression profiles, we were able to identify molecules which were differentially expressed by Tregs during parasitic infection and thereby might be involved in their immune-suppressive function. Moreover, we included CD4+CD25-Foxp3- T cells from spleens of non-infected and P. yoelii-infected mice in our analysis. It was proposed that immune-suppressive CD4+CD25-Foxp3- T cells might be induced during Plasmodium infection of mice. Thus, detailed gene expression data of these cells in comparison to CD4+CD25+Foxp3+ Tregs would contribute a better understanding in the phenotype.
Project description:Although several markers have been associated with the characterization of regulatory T cells (Treg) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Treg to control immunopathology has been demonstrated, we used the chronic helminth infection model S. mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling we first chose to study the localization and antigen-specific suppressive nature of classically defined Treg during infection. Presence of Foxp3+ cells were found especially in the periphery of granulomas and isolated CD4+CD25hiFoxp3+ Treg from infected mice blocked IFN-gamma and IL-10 cytokine secretion from infected CD4+CD25- effector T cells (Teff). Furthermore the gene expression patterns of Treg and Teff showed that in total 474 genes were significantly regulated during chronic schistosomiasis. Upon k-means clustering we identified genes exclusively regulated in all four populations including Foxp3, CD103, GITR, OX40 and CTLA-4: classical Treg markers. During infection however, several non-classical genes were up-regulated solely within the Treg population such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177 and Klrg1. Using RT-PCR we confirmed aspects of the microarray data and in addition showed that the expression profile of Treg from S. mansoni-infected mice is simultaneously unique and comparative with Treg derived from other infections Regulatory T cells (Treg) or effector T cells (Teff) were FACS-sorted as CD4+CD25+ or CD4+CD25- from mesenteric lymph nodes (MLN) of naive mice or from mice infected with Schistosoma mansoni. Affymetrix MOE430A 2.0 genechips were used to identify genes differentially expressed in Treg or Teff under resting or infected conditions.