Differential contributions of APC subsets to T cell activation in nonobese diabetic mice.
Despite the pivotal role of dendritic cells (DC) in shaping immunity, little is known about their functionality in type 1 diabetes. Moreover, due to the paucity of DC in vivo, functional studies have relied largely upon in vitro-expanded cells to elucidate type 1 diabetes-associated functional abnormalities. In this study, we provide a comprehensive analysis of the functional capabilities of in vivo-derived DC subsets from NOD mice by comparing DC to other NOD APC types and to DC from autoimmune-resistant strains. NOD DC closely resemble those from nonautoimmune strains with respect to costimulation and cytokine production. The exception is the CD8alpha(+)CD11b(-)DC subset which is numerically reduced in NOD spleens, but not in the pancreatic lymph nodes, while DC from both tissues produce little IL-12 in this strain. This defect results in unusual deferral toward macrophage-derived IL-12 in NOD mice; NOD macrophages produce aberrantly high IL-12 levels that can overcompensate for the DC defect in Th1 polarization. APC subset use for autoantigen presentation also differs in NOD mice. NOD B cells overshadow DC at activating islet-reactive T cells, whereas DC and B cells in NOD-resistant mice are functionally comparable. Differential involvement of APC subsets in T cell activation and tolerance induction may prove to be a crucial factor in the selection and expansion of autoreactive T cells.
Marleau
Annette M
AM
Department of Microbiology and Immunology, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Summers
Kelly L
KL
Singh
Bhagirath
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018664:Interleukin-12