KINETICS AND MECHANISM OF EFFECTOR FOCUS FORMATION IN THE LUNGS OF MICE VACCINATED WITH IRRADIATED CERCARIAE OF SCHISTOSOMA-MANSONI

The sequence of events involved in effector focus formation around cha llenge schistosomula in the lungs of mice vaccinated with radiation-at tenuated cercariae of Schistosoma mansoni has been characterized follo wing intravenous administration of lung stage larvae. Histopathologica l analysis of the lungs of vaccinated animals revealed that infiltrati ng cells were present around larvae within 24 h. The main increment in cell recruitment occurred between 2 and 4 days, with foci reaching ma ximal diameter on day 8. No additional infiltration of the airways was detected by bronchoalveolar sampling before day 4 when the maximum nu mber of cells, predominantly lymphocytes, was recovered. In contrast, responses in challenge control animals were relatively slight prior to day 12. IFN gamma was the major cytokine in airway cultures from vacc inated mice, the greatest increment in production coinciding with peak cell recruitment. A similar pattern of IFN-gamma mRNA expression was observed in whole lung extracts, highlighting the dominance of Th1 res ponses in the effector mechanism. The slow start to focus formation ma y be due to the need for antigen, released by the intravascular parasi te, to be translocated across the endothelium, processed by accessory cells and presented to the helper T cells which orchestrate the effect or mechanism. The delay is of the same order as the period of developm ent which the parasite must undergo in the lung, to facilitate further migration. This similarity in the timing may explain why some larvae are able to avoid the consequences of the pulmonary effector response.