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.
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
James
J
De Jersey
Danielle
D
Carmignac
Paul
P
Le Tissier
Thomas
T
Barthlott
Iain
I
Robinson
Brigitta
B
Stockinger
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