Neuroimmunology of the horse with special reference to equine protozoal myeloencephalitis

Equine Protozoal Myeloencephalitis (EPM) is a serious neurologic condition of the horse caused by the protozoan parasite Sarcocystis neurona . The parasite is found only within the central nervous system (CNS), where it causes inflammation and subsequent clinical neurologic disease. Persistent infections, chronicity, and recrudescence are hallmarks of the disease, suggesting that immune clearance of the organism might be compromised. Because the parasite resides within the nervous system, the activity of the immune system within the CNS tissue compartment is critical to resolution of infection.; It has been known for many years that the immune response within the CNS differs from that of peripheral tissues. The immune response is blunted, delayed type hypersensitivity (DTH) reactions are impaired, and immune globulin responses are altered. This has been referred to as the condition of "immune privilege". This altered immune response is believed to contribute to the persistence of Toxoplasma gondii in the brain. T. gondii is a very similar organism to S. neurona, and a similar phenomenon of immune privilege may contribute to its pathophysiology. The purpose of the studies reported herein, therefore, was to examine the nature of the immune response to S. neurona within the CNS of the horse.; The distribution of lymphocyte phenotype subsets within the cerebrospinal fluid (CSF) of normal and diseased horses was examined by flow cytometry, and CNS parenchymal lymphocyte distribution was evaluated by immunohistochemical labeling of T- and B-lymphocytes. These studies found that T cells predominate in the CSF (79.0% vs. 67.0% in peripheral blood), while T cells also predominate in the parenchymal lesions of the CNS due to S. neurona.; Further studies demonstrated that the CSF of horses contains the immunosuppressive cytokine TGF-beta2, and that its concentration is decreased in the CSF of horses with EPM (256 +/- 29 pg/ml vs. 144 +/- 38 pg/ml; mean +/- SEM). In addition, CSF from horses was found to stimulate the production of IFN-gamma when coincubated with peripheral blood mononuclear cells (PBMC's) and exposed to the plant lectin phytohemagglutinin-P (PHA-P). Blocking CSF TGF-beta2 with monoclonal antibodies enhanced the production of IFN-gamma, although not enough to achieve statistical significance. The sum results of these studies sheds light on the nature of the equine CNS immune response, and demonstrates that CSF has pro-inflammatory compounds and alters IFN-gamma response, perhaps by the action of TGF-beta 2. Further studies are warranted to determine the precise role of TGF-beta 2 and IFN-gamma in the immune response to S. neurona.