Conditional Silencing of H-2Db Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen–Specific CD8 T Cell Responses during Theiler's Virus Infection

Abstract

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Mouse Models of Experimental Glioblastoma

“…The role of each cell type in generating the CD8 + T cell responses was different. MHC I H2-K b or H-2D b antigen presentation by dendritic cells and macrophages in these model systems is non-redundant (30,31,115).…”

“…The first successful induced brain tumor was developed in 1939 with intracranial implantation of 20-methylcholanthrene into C3H mice subarachnoid by Seligman and Shear, which led to gliomas and meningeal fibrosarcomas (26). Even though chemical-induced glioblastoma models are now outdated, several mouse cell lines established from those tumors have been later used for allograft implantation mouse models (27)(28)(29)(30)(31). Rous sarcoma virus has been used to induce mouse glioblastoma since the 1960s (32)(33)(34).…”

“…Transplantation of tumor cells into mice can rapidly generate experimental glioblastoma model for studying tumor biology and examining therapeutic methods. Many types of biological materials can be transplanted into mice brain by intracranial implantation (31,109) or subcutaneous injection (110) techniques. This includes engineered murine tumor cells,such as GL261; engineered virus vaccines; Cre-LoxP, TAM/Tet/Dox induced tumor cells; and cancer cells/tissues from primary patient tumors (PDX).…”

Microglia and Perivascular Macrophages Act as Antigen Presenting Cells to Promote CD8 T Cell Infiltration of the Brain

“…Rediscovery of the glymphatic system in the CNS has allowed for improved understanding of how T cells are primed and activated against CNSderived antigens (11,12). Conceivably, T cells encounter cognate antigen once it has drained to the deep cervical lymph node, where antigen presenting cells (APCs) prime naïve T cells (13,14). However, activated T cells are restimulated by local APCs to infiltrate across the blood brain barrier (BBB) into the parenchyma.…”

“…However, mice deficient in CD8 T cells or lacking certain MHC class I haplotypes are unable to clear TMEV from the CNS, r esultin g in virus-induc ed demyelinating disease (29)(30)(31)(32). CD8 T cell activation, brain infiltration, and viral clearance are dependent on recognition of the immunodominant TMEV capsid protein-derived peptide VP2 121-130 presented in the H-2D b MHC class I molecule (13,30,31,33). The highly reproducible nature of this CD8 T cell response enables in vivo analysis of antigen presentation requirements for lymphocyte infiltration of the brain.…”