Two waves of γ δ T cells expressing different V δ genes are recruited into schistosome-induced liver granulomas

Abstract

Isolated granulomas provide a unique model to study T cells in the site of inflammation. Schistosoma mansoni-infected mice develop liver granulomas in response to schistosome egg deposition and the granulomas contain γ δ T cells that appear to be activated (Pgp-1high and L-selectin low). Analysis of kinetics and TCR gene usage of granuloma γ δ T cells revealed a limited TCR repertoire restricted to V γ 1.1, V δ 4, and V δ 6 genes, suggesting that the occurrence of γ δ T cells in the granuloma is influenced by TCR V gene usage. The V δ 4+, but not the V δ 6+, γ δ T cells expressed CD69, a marker of recent activation. To determine if there was a preferred order of accumulation of the γ δ T cells in granulomas, s.c. sponge grafts were implanted into schistosome-infected mice, schistosome eggs were injected into the grafts, and accumulated T cells were sequentially analyzed. The earliest γ δ T cell immigrants expressed V δ 6 and later immigrants expressed V δ 4 V genes. Additional evidence for a role of TCR specificity in the accumulation of γ δ T cells in granulomas is their absence from schistosome granulomas in TCR transgenic mice that express only a single MHC-specific γ δ TCR. Finally, γ δ T cell recruitment into the granulomas did not require β 2-microglobulin, since γ δ T cells were present in liver granulomas of β 2-microglobulin gene-disrupted mice. The analysis of the influx of γ δ T cells into schistosome-induced, liver granulomas and schistosome egg-containing sponges provides a model system to investigate the role, if any, of γ δ T cells in schistosome infections.