Two waves of gamma delta T cells expressing different V delta genes are recruited into schistosome-induced liver granulomas.
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 gamma delta T cells that appear to be activated (Pgp-1high and L-selectin low). Analysis of kinetics and TCR gene usage of granuloma gamma delta T cells revealed a limited TCR repertoire restricted to V gamma 1.1, V delta 4, and V delta 6 genes, suggesting that the occurrence of gamma delta T cells in the granuloma is influenced by TCR V gene usage. The V delta 4+, but not the V delta 6+, gamma delta T cells expressed CD69, a marker of recent activation. To determine if there was a preferred order of accumulation of the gamma delta 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 gamma delta T cell immigrants expressed V delta 6 and later immigrants expressed V delta 4 V genes. Additional evidence for a role of TCR specificity in the accumulation of gamma delta T cells in granulomas is their absence from schistosome granulomas in TCR transgenic mice that express only a single MHC-specific gamma delta TCR. Finally, gamma delta T cell recruitment into the granulomas did not require beta 2-microglobulin, since gamma delta T cells were present in liver granulomas of beta 2-microglobulin gene-disrupted mice. The analysis of the influx of gamma delta T cells into schistosome-induced, liver granulomas and schistosome egg-containing sponges provides a model system to investigate the role, if any, of gamma delta T cells in schistosome infections.
Sandor
M
M
Department of Pathology, College of Medicine, University of Iowa, Iowa City 52242, USA.
Sperling
A I
AI
Cook
G A
GA
Weinstock
J V
JV
Lynch
R G
RG
Bluestone
J A
JA
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D015870:Gene Expression; D006099:Granuloma / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D016130:Immunophenotyping; D008099:Liver / Q000469:parasitology / Q000473:pathology*; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency
D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing; D001613:beta 2-Microglobulin