Robert L. Hirsch

Measles encephalomyelitis. Clinical and immunologic studies

Abstract We studied 19 patients with postinfectious encephalomyelitis complicating natural measles-virus infections, and our results support the hypothesis that this demyelinating disease has a pathogenesis similar to that of experimental allergic encephalomyelitis. Early myelin destruction was demonstrated by the presence of myelin basic protein in cerebrospinal fluid, and lymphocyte proliferative responses to myelin basic protein were found in 8 of 17 patients tested. A lack of intrathecal synthesis of antibody against measles virus suggests that measles encephalomyelitis may not be dependent on virus replication within the central nervous system. Similar lymphoproliferative responses to myelin basic protein of lymphocytes from single patients with encephalomyelitis after rabies vaccine or after varicella or rubella virus infections suggest a common immune-mediated pathogenesis for the perivenular demyelinating disease that can follow the injection of neural tissues or infection by a variety of viruses....

Cellular immune responses during complicated and uncomplicated measles virus infections of man

Lymphocytes from patients with measles showed profound and prolonged suppression of proliferative responses to mitogens. The degree of suppression was similar in patients with uncomplicated measles virus infection and in those with pneumonia or postinfectious encephalitis. Despite this suppression, lymphocyte responses to measles antigen and PPD were demonstrated in patients with encephalitis and uncomplicated disease, even early in infection. Most patients with pneumonia did not have demonstrable antigen-specific responses. The proportions of T helper (OKT 4) and T suppressor (OKT 8) cells and functional tests of Con A suppressor cell activity showed no significant difference between control and measles patients but, in contrast to controls, cells from measles patients cultured in the absence of any stimulant significantly suppressed the proliferation of allogeneic responder cells. Nine of 20 supernatant fluids from these cultures possessed a soluble suppressor factor. These studies indicate varied disruptions of immune reactivity during measles.

Measles virus vaccination of measles seropositive individuals suppresses lymphocyte proliferation and chemotactic factor production.

Abstract Measles virus vaccination of adults seropositive for measles resulted in suppression of chemotactic factor production in response to concanavalin A (Con A), purified protein derivative (PPD), and purified measles virus antigen, and of lymphoproliferative responses to high doses of phytohemagglutinin (PHA). Persons receiving the vaccine had no clinical signs of infection, no detectable viremia, and no rise in antibody titers to measles virus. The suppression of both chemotactic factor production and lymphoproliferation was of shorter duration than that observed in studies of acute measles virus infection. Suppression could not be related to increases in the number of circulating cells capable of suppressing the Con A or PHA responses of normal lymphocytes. These studies indicate that measles virus may cause immunosuppression in the absence of detectable virus replication in mononuclear cells.

Immune responses to acute alphavirus infection of the central nervous system: Sindbis virus encephalitis in mice.

Publisher Summary Sindbis virus is an alphavirus that produces an acute nonfatal encephalitis in mice. The local immune responses to this virus are both cellular and humoral. The cellular response is characterized by an infiltration of mononuclear cells into the cerebrospinal fluid (CSF), the meninges, and the brain parenchyma. This inflammatory response is initiated by sensitized T-lymphocytes that are stimulated by exposure to viral antigen to produce a lymphokine, which is chemotactic for mononuclear cells. These T-cells may also produce a lymphokine that stimulates mast cells to release vasoactive amines, which facilitate monocyte entry from the blood. Inflammation is not necessary for clearance of virus from the brain. Humoral immune responses are initially systemic and, in the central nervous system (CNS), reflect transudation of serum antibody. During recovery, there is local production of antiviral IgA as well as IgG.