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Allergy and Immunology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Granuloma formation and its regulation are dependent on
lymphocytes. Therefore, we compared the characteristics of lymphocytes
derived from the spleens and granulomas of Schistosoma
mansoni-infected mice during the course of their disease. We
examined lymphocyte cell cycle kinetics, migration, expression of
activation Ags (CD69 and IL-2R), cytokine production (IL-2, IL-4,
IFN-
), and apoptosis. Lymphocytes in the G2/M phase of
the cell cycle and high levels of lymphocyte intracellular IL-2 were
found in the spleen but not in the granuloma. Cell trafficking
experiments showed Ag-specific recruitment of schistosomal egg Ag
(SEA)-reactive lymphoblasts into granulomas in vivo, as well as
recruitment to, residence within, and egress from granulomas in vitro.
Granuloma-derived lymphocytes were more highly activated than splenic
lymphocytes based on higher levels of CD69 and IL-2R expression. While
the granuloma microenvironment was rich in Th2 cytokines, during peak
granuloma formation, the lymphocytes per se from the spleen and
granuloma did not exhibit a dominant Th1 or Th2 cytokine profile,
producing low but similar levels of IL-4 and IFN-. The discrepancy
between high IL-2R expression and low levels of IL-2 protein production
by granuloma lymphocytes was associated with increased apoptosis in the
granuloma compared with the spleen. These findings support the
hypothesis that granulomas may play a role in the regulation of
systemic pathology in schistosomiasis by adversely affecting the
survival of SEA-reactive, immunopathogenic T
lymphocytes.
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