Differential response of human naive and memory/effector T cells to dendritic cells infected by respiratory syncytial virus

In vitro studies have contributed substantially to the understanding of immunopathology of respiratory syncytial virus (RSV)-mediated disease. In the present study we compared the effect of RSV-infected dendritic cells on the time-course of the primary and memory/effector T cell response in vitro. Cultures with uninfected dendritic cells known to elicit T helper 2 (Th2) responses and with polyinosinic-polycytidylic acid (poly-IC)-stimulated dendritic cells known to elicit Th1 responses served as controls. At day 1 after stimulation there was a high proportion of interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha-producing T cells with no difference in number of producing T cells as well as concentration of secreted cytokines between RSV-infected and control cultures. However, up to day 3 generation of IFN-gamma was reduced markedly. In addition, there was a reduced proliferation in RSV cultures. At day 7 the RSV-treated cultures showed a preponderance of IL-4 generation. At days 21-24, after three rounds of restimulation, memory/effector T cells matured under the influence of RSV were still not fully polarized but in contrast to the primary response displayed a predominance of Th1 cytokines. Contact with RSV-infected HEp-2 cells inhibited proliferation of T cells; memory effector T cells were less sensitive to contact inhibition than naive T cells. In addition, RSV inhibited the stimulated rearrangement of cortical actin more effectively in naive compared to memory T cells. In summary, we have shown that RSV infection of dendritic cells has a distinct modulatory effect on the primary response and a less pronounced effect on the memory response.