Regulation of lymphocyte proliferation after influenza virus infection of human mononuclear leukocytes.

Previous studies demonstrated that in vitro infection with influenza A viruses altered several functions of human monocytes-macrophages but did not detectably alter functions of human lymphocytes. However, both types of cells were infected, as determined by production and surface expression of viral antigens. In the current studies, human mononuclear leukocytes were infected in vitro and assayed for both influenza virus-induced proliferation and mitogen (phytohemagglutinin [PHAl)-induced proliferation, as well as for ability to stimulate proliferative responses by normal autologous leukocytes. The leukocytes showed proliferation in response to the infectious virus, but concomitant depressed proliferative responses to PHA. Coculture experiments suggested suppression of PHA-induced responses by the virus-infected cells. However, upon coculture with fresh autologous leukocytes (without PHA stimulation), both virus-infected macrophages and virus-infected lymphocytes induced autologous lymphocyte proliferative responses. Altered proliferative responses to mitogen stimulation after exposure to the virus were not due to diminished interleukin-1 production or diminished expression of HLA-DR by monocytes-macrophages. The expression of influenza virus antigens and resulting induction of autologous proliferative responses, combined with depressed mitogen-induced proliferation, may be important in human antiviral defense.