sirolimus and Arenaviridae-Infections

Asymmetric partitioning of fate determinants is a mechanism that contributes to T cell differentiation. However, it remains unclear whether the ability of T cells to divide asymmetrically is influenced by their differentiation state, as well as whether enforcing asymmetric cell division (ACD) rates would have an impact on T cell differentiation and memory formation. Using the murine LCMV infection model, we established a correlation between cell stemness and the ability of CD8

Topics: Animals; Arenaviridae Infections; Asymmetric Cell Division; CD8-Positive T-Lymphocytes; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation; Hematopoietic Stem Cells; Humans; Immunologic Memory; Immunotherapy, Adoptive; Lymphocytic choriomeningitis virus; Mice; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

Hemophagocytic lymphohistiocytosis (HLH) is an immunodysregulatory disorder for which more effective treatments are needed. The macrolide rapamycin has immunosuppressive properties, making it an attractive candidate for controlling the aberrant T cell activation that occurs in HLH. To investigate its therapeutic potential, we used rapamycin to treat Lymphocytic Choriomeningitis Virus (LCMV)-infected perforin-deficient (Prf1(-/-)) mice according to a well-established model of HLH. At the regimens tested, rapamycin did not improve weight loss, splenomegaly, hemophagocytosis, cytopenias, or proinflammatory cytokine production in LCMV-infected Prf1(-/-) animals. Thus, single agent rapamycin appears ineffective in treating the clinical and laboratory manifestations of LCMV-induced HLH.

Topics: Animals; Arenaviridae Infections; Cell Separation; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunosuppressive Agents; Lymphocytic choriomeningitis virus; Lymphohistiocytosis, Hemophagocytic; Mice; Mice, Inbred C57BL; Mice, Knockout; Perforin; Sirolimus