Lyme Arthritis Synovial γδ T Cells Instruct Dendritic Cells via Fas Ligand

Abstract CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant γδ T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of γδ T cells as well as in IFN-γ, TNF-α, and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-γ, TNF-α, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired γδ T-cell expansion. IFN-γ production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-α. Conversely, addition of recombinant IL-1β, TNF-α, or both further enhanced IFN-γ production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ γδ T cells, which may be harnessed for immunotherapy.

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A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis.

Journal of Experimental Medicine ◽

10.1084/jem.183.4.1789 ◽

1996 ◽

Vol 183 (4) ◽

pp. 1789-1796 ◽

Cited By ~ 476

Author(s):

G Süss ◽

K Shortman

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cd4 T Cells ◽

Fas Ligand ◽

Activated T Cells ◽

T Cell Apoptosis ◽

Peripheral T Cells ◽

Surface Staining ◽

Induced Apoptosis ◽

Antigen Presenting

Dendritic cells (DC), the most efficient antigen-presenting cells, are well equipped for activation of naive CD4+ T cells by their expression of high levels of major histocompatibility complex and costimulator molecules. We now demonstrate that some DC are equally well equipped for killing these same T cells. Murine splenic DC consist of both conventional CD8alpha- DC and a major population of CD8alpha+ DC. Whereas CD8- DC induce a vigorous proliferative response in CD4 T cells, CD8+ DC induce a lesser response that is associated with marked T cell apoptosis. By using various mixtures of T cells and DC from Fas-mutant lpr/lpr mice and Fas-ligand (FasL) mutant gld/gld mice, we show this death is due to interaction of Fas on activated T cells with FasL on CD8+ DC. Furthermore, we show by direct surface staining that CD8+ DC, but not CD8- DC, express FasL at high levels. These findings indicate that FasL+ CD8+ DC are a specialized subgroup of DC with a role in the regulation of the response of primary peripheral T cells.

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Major Histocompatibility Complex Class II-Independent Generation of Neutralizing Antibodies against T-Cell-Dependent Borrelia burgdorferi Antigens Presented by Dendritic Cells: Regulation by NK and γδ T Cells

Infection and Immunity ◽

10.1128/iai.69.4.2407-2415.2001 ◽

2001 ◽

Vol 69 (4) ◽

pp. 2407-2415 ◽

Cited By ~ 11

Author(s):

M. Lamine Mbow ◽

Nordin Zeidner ◽

Robert D. Gilmore ◽

Marc Dolan ◽

Joseph Piesman ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Major Histocompatibility Complex ◽

Borrelia Burgdorferi ◽

Mhc Class Ii ◽

Γδ T Cells ◽

Humoral Response ◽

Class Ii ◽

Histocompatibility Complex ◽

Mhc Class Ii Molecules

ABSTRACT We previously showed that adoptive transfer of Borrelia burgdorferi-pulsed dendritic cells (DCs) into syngeneic mice protects animals from challenge with tick-transmitted spirochetes. Here, we demonstrate that the protective immune response is antibody (Ab) dependent and does not require the presence of major histocompatibility complex (MHC) class II molecules on DCs. Mice sensitized with B. burgdorferi-pulsed MHC class II-deficient (MHC class II−/−) DCs mounted a humoral response against protective antigens, includingB. burgdorferi outer surface protein A (OspA) and OspC. B-cell help for the generation of neutralizing anti-OspC immunoglobulin G Abs could be provided by γδ T cells. In contrast, anti-OspA Ab production required the presence of αβ T cells, although this pathway could be independent of MHC class II molecules on antigen-presenting cells. Moreover, depletion of NK cells prior to transfer of antigen-pulsed MHC class II−/− DCs resulted in significant increases in the levels of neutralizing Abs induced by DCs. Altogether, these data suggest that the initial interactions between DCs and innate immune cells, such as γδ and NK cells, can influence the generation of a protective humoral response againstB. burgdorferi antigens.

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