High expression of Fas ligand by synovial fluid-derived gamma delta T cells in Lyme arthritis.
Gamma delta T cells accumulate at epithelial barriers and at sites of inflammation in various infectious and autoimmune diseases, yet little is understood about the function of tissue-infiltrating gamma delta T cells. We observe that gamma delta T cells of the V delta 1 subset accumulate in synovial fluid of human Lyme arthritis and are intensely cytolytic toward a wide array of target cells. Particularly striking is that the cytolytic activity is highly prolonged, lasting for at least 3 wk after stimulation of the gamma delta T cells with Borrelia burgdorferi. Cytolysis is largely Fas dependent and results from very high and prolonged expression of surface Fas ligand, which is transcriptionally regulated. This also manifests in a substantial level of self-induced apoptosis of the gamma delta T cells. In this capacity, certain gamma delta T cell subsets may serve as cytolytic sentinels at sites of inflammation, and perhaps at epithelial barriers.
Roessner
Karen
K
Department of Medicine (Immunobiology), The University of Vermont College of Medicine, Burlington, VT 05405, USA.
Wolfe
Julie
J
Shi
Cuixia
C
Sigal
Leonard H
LH
Huber
Sally
S
Budd
Ralph C
RC
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D025065:Borrelia burgdorferi / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008193:Lyme Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor; D054353:Perforin