Lyme arthritis synovial gammadelta T cells instruct dendritic cells via fas ligand.
gammadelta T cells participate in the innate immune response to a variety of infectious microorganisms. They also link to the adaptive immune response through their induction of maturation of dendritic cells (DC) during the early phase of an immune response when the frequency of Ag-specific T cells is very low. We observe that in the presence of Borrelia burgdorferi, synovial Vdelta1 T cells from Lyme arthritis synovial fluid potently induce maturation of DC, including production of IL-12, and increased surface expression of CD40 and CD86. The activated DC are then able to stimulate the Vdelta1 T cells to up-regulate CD25. Both of these processes are initiated primarily by Fas stimulation rather than CD40 activation of DC via high expression of Fas ligand by the Vdelta1 T cells. DC are resistant to Fas-induced death due to expression of high levels of the Fas inhibitor c-FLIP. This effect serves to divert Fas-mediated signals from the caspase cascade to the ERK MAPK and NF-kappaB pathways. The findings affirm the importance of the interaction of certain T cell populations with DC during the early phases of the innate immune response. They also underscore the view that as levels of c-FLIP increase, Fas signaling can be diverted from induction of apoptosis to pathways leading to cell effector function.
Collins
Cheryl
C
Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington, VT 50405, USA.
Wolfe
Julie
J
Roessner
Karen
K
Shi
Cuixia
C
Sigal
Leonard H
LH
Budd
Ralph C
RC
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D023201:CD40 Ligand / Q000032:analysis; D003713:Dendritic Cells / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008193:Lyme Disease / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000502:physiology*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D048069:Tumor Necrosis Factors; D023201:CD40 Ligand; D018664:Interleukin-12; D048049:Extracellular Signal-Regulated MAP Kinases