Immunology 113(4): 482-490

Site-specific regulation of tissue dendritic cell function by granulocyte–macrophage colony-stimulating-factor

School of Biological Sciences, University of Manchester, Manchester, UK

Correspondence: Dr P. J. Wood, School of Biological Sciences, University of Manchester, 3·239 Stopford Building, Oxford Road, Manchester, M13 9PT, UK. E-mail: ku.ca.nam@doow.j.retep

School of Biological Sciences, University of Manchester, Manchester, UK

Received 2004 May 13; Revised 2004 Aug 2; Accepted 2004 Aug 6.

Abstract

Tissue dendritic cells (DC) are usually associated with phagocytic function but poor T-cell immunostimulatory capacity. Following activation, dendritic cells are stimulated to leave tissue sites and migrate to lymphoid tissue, acquiring immunostimulatory capacity during the process. We provide evidence that the immunostimulatory capacity of tissue DC, but not spleen cells, can be affected in situ by granulocyte–macrophage colony-stimulating-factor (GM-CSF). Initially it was found that islet cells from non-obese diabetic and BALB/c mice, which produce GM-CSF, showed significantly higher immunostimulatory capacity than islets from C3H and C57BL/6 mice, which do not produce GM-CSF. Second, pretreatment of nonobese diabetic mice with anti-GM-CSF antibody significantly reduced the immunostimulatory capacity of islet cells, but not spleen cells, although it had no effect on the numbers of cells expressing DC-associated antigens. Therefore the immunostimulatory function of islet DC is partially dependent on GM-CSF. By contrast, spleen DC immunostimulatory function does not show the same dependence on GM-CSF. This may affect the ability of dendritic cells to stimulate autoimmune responses or tolerance.

Keywords: dendritic cells, granulocyte–macrophage colony-stimulating factor, T-cell stimulation, islets of Langerhans

Abstract

NOD mice received i.p. injections of 100 µg of α-GM-CSF mAb (31G6) or rat IgG 5, 3 and 1 day before removal of the pancreas for immunocytochemical staining for CD11c (N418), DEC-205 (NLDC-145) and CD8^(53-C.7).

Acknowledgments

This work was supported by the Diabetes UK (P.W.) and a Medical Research Council studentship (J.L.).

Acknowledgments

Abbreviations

APC	antigen presenting cell
DC	dendritic cell
GM-CSF	granulocyte–macrophage colony-stimulating-factor
mAb	monoclonal antibody
NOD	non-obese diabetic

Abbreviations

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