MONOCYTE CHEMOTACTIC PROTEIN EXPRESSION DURING SCHISTOSOME EGG GRANULOMA-FORMATION - SEQUENCE OF PRODUCTION, LOCALIZATION, CONTRIBUTION, AND REGULATION

The present study explored the role of murine monocyte chemotactic pro tein (MCP) in the T cell-mediated hypersensitive granulomatous respons e to Schistosoma mansoni eggs. The study examined the time course of l ocal production, contribution to cellular infiltration, and the role o f T cells in endogenous regulation. Synchronized pulmonary granulomas were conditions or primary and secondary states of immunity. Primer-di rected polymerase chain reaction analysis showed increased MCP mRNA ex pression in granulomatous lungs, mainly in the secondary response. Lev els of MCP were measured by enzyme-linked immunosorbent assay in cultu res of intact granulomas. Spontaneous MCP production was modest in pri mary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accele rated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistoche mical staining revealed the strongest MCP expression within microvascu lar adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% r eduction in the secondary granuloma area but did not significantly aff ect the primary response. With adoptive cell transfer and T cell subse t depletion, it was shown that Thy-1(+) and CD5(+) cells augmented, wh ereas CD8(+) cells appeared to impair, MCP production. This provides d irect evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.