Publications

Oligodendroglioma is one of the most common primary central nervous system neoplasms of dogs. It is often diagnosed in older, brachycephalic breeds, and although its typical clinical features and neuroanatomic location have been well described, less common presentations may hinder its diagnosis. We describe 3 cases of canine cerebral oligodendroglioma that clinically and grossly present as intraventricular tumors. Histologic findings in all cases were typical of oligodendroglioma. Neoplastic cells were uniformly immunoreactive for Olig2 and negative for neuron-specific enolase, neurofilament, and glial fibrillary acidic protein. In addition to the immunopositivity for Olig2, a cluster of morphologically distinct neoplastic cells in one of the cases was immunoreactive for synaptophysin, and the case was diagnosed as an oligodendroglioma with neurocytic differentiation. Based on these findings, oligodendroglioma should be included as a differential diagnosis for intraventricular neoplasia in dogs. Furthermore, oligodendroglioma with ventricular involvement should be differentiated from central neurocytoma by immunohistochemistry.

Chronic infections induce a complex immune response that controls pathogen replication, but also causes pathology due to sustained inflammation. Ca2+ influx mediates T cell function and immunity to infection, and patients with inherited mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we demonstrate that STIM1 is required for T cell-mediated immune regulation during chronic Mtb infection. Compared with WT animals, mice with T cell-specific Stim1 deletion died prematurely during the chronic phase of infection and had increased bacterial burdens and severe pulmonary inflammation, with increased myeloid and lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly reduced IFN-γ production during the early phase of Mtb infection, bacterial growth was not immediately exacerbated. During the chronic phase, however, STIM1-deficient T cells displayed enhanced IFN-γ production in response to elevated levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with impaired activation-induced cell death upon repeated TCR engagement and pulmonary lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb-infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells (iTregs) due to a T cell-intrinsic requirement for STIM1 in iTreg differentiation and excessive production of IFN-γ and IL-12, which suppress iTreg differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell-mediated immune regulation to limit injurious inflammation during chronic infection.