Measles remains a major worldwide health problem due to problems with delivery, acceptance and timing of measles immunization. In addition, measles cases have been increasing in the U.S. in association with waning immunity after appropriate immunization. The primary complications of measles are pneumonia, diarrhea and postinfectious encephalomyelitis. The effect of measles on the immune system is though to be important in the development of these complications. Skin test responses and mitogen-induced lymphoproliferative responses are depressed for weeks in association with infection. At the same time, the immune response to measles virus during natural infection is effective in clearing virus from tissue and in establishing lifelong immunity to reinfection. Our studies have determined that there is immune system activation during the period of """"""""immune suppression"""""""". We have also determined that a defect in production of IL-2 contributes to the failure of T cells to proliferate in response to in vitro mitogen stimulation. To further define the relationship between measles and functional alterations in the immune system the following specific aims are proposed: (1) To identify the mononuclear cells infected by measles virus in vivo. (2) To define the in vivo state of activation and patterns of cytokine production of T cells and subsets of T cells during measles. (3) To define the state of T cell unresponsiveness and determine the similarity of this unresponsive state to that induced by lack of co-stimulatory signals from antigen presenting cells. (4) To determine the proliferative responses of T cells to alternative and supplementary stimuli. (5) To determine the role of production of inhibitors of proliferation to T cell unresponsiveness in vitro. (6) To determine whether the lack of natural killer (NK) cell activity during measles is due to lack of NK cells or to an inability of NK cells to lyse target cells. (7) To identify the immune cells present in areas of measles virus-induced inflammation and in brain during postmeasles encephalomyelitis.
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