Effect of in Vitro Virus Infection on Response of Human Monocytes and Lymphocytes to Mitogen Stimulation

Abstract

Viral infection and immunization can depress certain immune functions, including in vitro transformation response of lymphocytes to mitogens and antigens. Since optimal lymphocyte response occurs only in the presence of macrophages, we sought to determine whether the depression of transformation response could result from macrophage dysfunction induced by the viral infection. Highly purified human macrophages and lymphocytes were infected in vitro with influenza A virus. There was no significant difference in transformation response between uninfected and infected lymphocytes either alone or when combined with uninfected macrophages, suggesting, by exclusion, a macrophage defect. Direct evidence for macrophage dysfunction was provided by the observation that virus-infected macrophages were significantly less effective than uninfected macrophages in enhancing the transformation response of either uninfected (p < 0.025) or infected (p < 0.01) lymphocytes. Adverse effects of virus infection could not be attributed to an effect of the virus cultivation medium, to cell separation procedures, or to changes in cell viability. Adverse effects on macrophage function were evident as early as 24 hr after virus infection and were directly related to the virus inoculum. Depressed enhancement of response by macrophages was demonstrated to a greater extent with suboptimal than optimal dose phytohemagglutinin stimulation, and was shown by using allogenic as well as autologous macrophages. Macrophage phagocytosis of staphylococci was similarly depressed but not eliminated by virus infection. Depressed transformation of unseparated mononuclear leukocytes was only manifested when virus infection occurred before or at the time of phytohemagglutinin stimulation, again suggesting a primary effect on macrophages. The inability of virus-infected human macrophages to enhance lymphocyte response to mitogen can account for the depression of human lymphocyte transformation seen during influenza virus infection. Viral infection had no adverse effect on lymphocyte response per se.