RHINOVIRUS PRODUCES NONSPECIFIC ACTIVATION OF LYMPHOCYTES THROUGH A MONOCYTE-DEPENDENT MECHANISM

There is evidence that rhinovirus (RV) infections are frequent causes of increased asthmatic symptoms and can specifically enhance allergic inflammation in the airway. To further define effects of RV infection on cellular immunity, we have begun to develop in vitro models for stu dy. When human PBMC were incubated with S-35-labeled RV16, specific bi nding via ICAM-1 on monocytes was observed. Incubation of PBMC with RV also led to a dose-related increase in the expression of the early ac tivation marker CD69 on 30 to 70% of T cells. The RV16-induced increas es in CD69 were blocked by anti-ICAM-1 mAb, and were not elicited by U V-inactivated (noninfectious) virus. The degree of CD69 enhancement co rrelated with the number of monocytes in mixtures of PBMC, did not occ ur in monocyte-depleted cultures, and was mediated by one or more solu ble factor(s). RV also induced secretion of IFN-gamma from both periph eral blood T cells and NK cells, and IFN-gamma mRNA was greatest in T cells that were CD69(+). Finally, supernatant from RV-activated CD3(+) CD69(+) cells had biologic activity that promoted eosinophil survival in vitro; this RV16-associated activity was blocked when co-incubation s were performed with IFN-gamma mAbs. These observations suggest that RV nonspecifically activates a large proportion of T cells through a m onocyte-dependent mechanism. Such changes in vivo could enhance airway inflammation, and this may include effects on inflammatory cells in t he airways of allergic individuals.