Activation of CD8 T cells by antigen expressed in the pituitary gland.
Ag expressed exclusively in the anterior pituitary gland and secreted locally by pituitary somatotrophs can gain access to the MHC class I presentation pathway and activate CD8 T cells. Influenza nucleoprotein (NP) was expressed as a transgene under the control of the human growth hormone (GH) locus control region. Activation of monoclonal F5 CD8 T cells specific for NP resulted in spontaneous autoimmune pathology of the pituitary gland in mice transgenic for both NP and the F5 TCR. Destruction of somatotrophs resulted in drastically reduced GH levels in adult mice and a dwarf phenotype. Adoptive transfer of F5 T cells into NP-transgenic hosts resulted in full T cell activation, first demonstrable in regional lymph nodes, followed by their migration to the pituitary gland. Despite the presence of activated, IFN-gamma-producing CD8 T cells in the pituitary gland and a slight reduction in pituitary GH levels, no effect on growth was observed. Thus, CD8 T cells have access to the neuroendocrine system and get fully activated in the absence of CD4 help, but Ag recognition in this location causes autoimmune pathology only in the presence of excessive CD8 T cell numbers.
de Jersey
James
J
Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London, United Kingdom.
Carmignac
Danielle
D
Barthlott
Thomas
T
Robinson
Iain
I
Stockinger
Brigitta
B
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000956:Antigens, Viral / Q000096:biosynthesis / Q000502:physiology*; D001324:Autoantigens / Q000096:biosynthesis / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D013006:Growth Hormone / Q000096:biosynthesis; D009980:Influenza A virus / Q000276:immunology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D016601:RNA-Binding Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000637:transplantation; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000956:Antigens, Viral; D001324:Autoantigens; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D013006:Growth Hormone