Abortive activation precedes functional deletion of CD8+ T cells following encounter with self-antigens expressed by resting B cells in vivo.
InsHA mice express the haemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8) as a self antigen on pancreatic islet beta cells. We have utilized these mice to investigate the ability of resting B cells expressing Kd to induce self-tolerance among naive KdHA-specific clone 4 CD8+ T cells. Adoptive transfer of KdHA-peptide-pulsed resting B cells into clone 4-->InsHA recipients resulted in the activation and proliferation of clone 4 CD8+ T cells throughout the peripheral lymphoid tissues. Significantly, proliferation was not associated with the acquisition of T cell effector function; as evidenced by a lack of interferon-gamma production and the complete absence of any autoimmune pathology even after immunization of recipient mice with PR8. These data demonstrate that resting B cells pulsed with self-epitopes can induce abortive activation of potentially self-reactive naive CD8+ T cells resulting in their functional deletion from the peripheral T-cell repertoire in the absence of any associated autoimmunity.
Fraser
Joanne M
JM
University of Minnesota, Department of Gastroenterology Medicine, Minneapolis, MN, USA.
Janicki
Claire N
CN
Raveney
Ben J E
BJ
Morgan
David J
DJ
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017634:Self Tolerance; D018800:Thy-1 Antigens / Q000235:genetics
D001324:Autoantigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D007371:Interferon-gamma