T cells are unresponsive to transgenic MHC class II molecules expressed on pancreatic beta cells.
It has been proposed that the autoimmune attack on the pancreatic beta cells leading to insulin-dependent diabetes mellitus can be caused by the expression of MHC class II molecules on the beta cells. Transgenic mice expressing normal levels of allogeneic MHC class II Ak on the beta-cell surface (IP-Ak) do not develop either insulitis or diabetes, yet these mice are not tolerant to Ak when expressed on normal antigen-presenting cells. The authors have stimulated T cells from IP-Ak mice in vitro with Ak-expressing beta cells. Mice were also primed in vivo in order to facilitate the antiallogeneic response. The authors found that neither IP-Ak positive nor IP-Ak negative mice were able to respond to Ak-expressing beta cells, and that in vivo priming does not overcome this inability. They suggest that beta cells do not act as antigen-presenting cells, probably due to inability of delivering costimulatory signals. This strengthens the notion that MHC class II expression per se is not sufficient to induce an autoimmune attack on the beta cells.
Pilström
B
B
Department of Immunology, Wenner-Gren Institute, Stockholm University, Sweden.
Böhme
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens