T cell derived cytokines in lung-phase immunity to Schistosoma mansoni

Abstract

In C57Bl/6 strain mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni immune elimination of challenge parasites occurs in the lungs. Leucocytes were recovered from the lungs of such mice by bronchoalveolar lavage and cultured in vitro with larval antigen; the profile of cytokines released was then analyzed. From 14 days after vaccination, BAL cultures contained infiltrating lymphocytes which produced abundant quantities of IFN-g and IL-3. Challenge of vaccinated mice resulted in a second influx of IFN-g and IL-3--producing cells, earlier than after vaccination or in the appropriate controls. Ablation studies revealed that CD4+ T cells were the source of IFN-g. The timing of cytokine production after vaccination, and challenge was coincident with the phases of macrophage activation previously reported. At no time could lymphocytes in BAL cultures be stimulated to proliferate with either larval Ag or mitogen, in contrast to splenocytes from the same mice. Furthermore, T cell growth factor activity was not detected in BAL cultures stimulated with Ag. We suggest that the lymphocytes recruited to the lungs are memory/effector cells. When Ag released from challenge schistosomula is presented to these cells, they respond by secreting cytokines which mediate the formation of cellular aggregates around the parasites, blocking their onward migration.