Factors affecting the susceptibility of the mouse pituitary gland to CD8 T-cell-mediated autoimmunity.
We have previously shown, in a transgenic mouse model, that the pituitary gland is susceptible to CD8 T-cell-mediated autoimmunity, triggered by a cell-specific model autoantigen, resulting in pan-anterior pituitary hypophysitis and dwarfism. In the present study, we now demonstrate that antigen dose, the T-cell precursor frequency, the degree of lymphopenia and the context of target antigen expression, are important parameters determining the time course and extent of the pathological consequences of CD8 T-cell-mediated autoimmunity. Furthermore, our data indicate that the pituitary gland is susceptible to CD8 autoimmunity following an inflammatory insult such as a viral infection. As lymphocytic hypophysitis may be manifest in other autoimmune conditions, and the pituitary gland may be susceptible to T-cell-mediated pathology after immunization with a virus expressing soluble pituitary antigen, it is important to consider that strategies based on vaccination against soluble pituitary gonadotrophins could have other unexpected endocrine consequences.
De Jersey
James
J
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Carmignac
Danielle
D
Le Tissier
Paul
P
Barthlott
Thomas
T
Robinson
Iain
I
Stockinger
Brigitta
B
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D013006:Growth Hormone / Q000172:deficiency / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000032:analysis; D009976:Orthomyxoviridae Infections / Q000276:immunology; D010641:Phenotype; D010900:Pituitary Diseases / Q000276:immunology; D010903:Pituitary Gland, Anterior / Q000276:immunology*; D016601:RNA-Binding Proteins; D011863:Radioimmunoassay / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014758:Viral Core Proteins / Q000032:analysis
D016827:CD8 Antigens; D000939:Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D014758:Viral Core Proteins; D013006:Growth Hormone