Generation of allospecific cytolytic T-lymphocytes stimulated by pure pancreatic beta-cells in absence of Ia+ dendritic cells.
A murine mixed islet-lymphocyte coculture system (MILC) was used to quantitate the immunogenicity of a pure population of pancreatic beta-cells to more clearly define whether stimulator major histocompatibility complex (MHC) class II-positive dendritic cells are a major component leading to islet immunogenicity. Pancreatic beta-cells express MHC class I antigen but not class II antigen. These experiments compared the in vitro immunogenicity of fluorescence-activated cell sorted (FACS-IV) pure beta-cells (MHC class I-positive cells only) relative to unpurified dispersed islet cells (MHC class I-positive cells and class II-positive cells). The results demonstrated the surprising finding that pure DBA/2J (H-2d) pancreatic beta-cells stimulated a strong cytotoxic T-lymphocyte (CTL) response when exposed to C57BL/6 (H-2b) allosplenocytes in the MILC, similar to DBA/2J nonpurified dispersed islet cells. Furthermore, the stimulation of CTL by both purified beta-cells and nonpurified dispersed islet cells was blocked by addition of MHC-specific anti-class I monoclonal antibody directed against stimulator MHC antigen. The data imply that the highly immunogenic MHC class II-positive passenger leukocytes present in the islets were not necessary for the generation of the immune response in the presence of MHC class I-positive beta-cells. Although most of the pretreatment regimens attempting to decrease islet immunogenicity have been directed at eliminating the MHC class II-positive passenger leukocytes from the islets, this work suggests that modulation of MHC class I antigen may be an important approach.
Stock
P G
PG
Department of Surgery, University of Minnesota, Minneapolis.
Meloche
M
M
Ascher
N L
NL
Chen
S
S
Bach
F H
FH
Sutherland
D E
DE
D000818:Animals; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007126:Immunoglobulin Allotypes; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes