title: Involvement of PIT-1-reactive cytotoxic T lymphocytes in anti-PIT-1 antibody syndrome.
abstract: BACKGROUND
  Anti-pituitary-specific transcriptional factor 1 (PIT-1) antibody syndrome is characterized by acquired growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies associated with circulating anti-PIT-1 antibodies. Although autoimmunity to PIT-1 has been suggested as a pathogenesis, the precise mechanism of the syndrome remains unclarified.
  
  
  OBJECTIVE
  To elucidate the involvement of antibody- or cell-mediated immunity in anti-PIT-1 antibody syndrome.
  
  
  METHODS
  To investigate a direct effect of anti-PIT-1 antibody on pituitary cells, cell proliferation, and cytotoxicity detection assays were performed using patient serum. Enzyme-linked immunospot (ELISpot) assay was performed to evaluate the involvement of PIT-1-reactive cytotoxic T lymphocytes (CTLs). An immunohistochemical analysis using anti-CD4 or anti-CD8 antibody was performed to examine tissue infiltration by CTLs.
  
  
  RESULTS
  Patient serum did not exhibit any inhibitory effect on cell proliferation and secretion of GH and PRL in GH3 cells. In addition, complement-dependent cytotoxicity was not detected in patient serum on GH3 cells or primary pituitary cells. The ELISpot assay revealed the presence of CTLs that specifically reacted to the recombinant PIT-1 protein in the patient's peripheral lymphocytes. CD8(+) cell infiltrations, which is the characteristic of CTLs, were observed in the pituitary gland, adrenal gland, stomach, thyroid gland, liver, and pancreas of the patient with anti-PIT-1 antibody syndrome.
  
  
  CONCLUSIONS
  These results suggest that the anti-PIT-1 antibody is not a cause but a marker of anti-PIT-1 antibody syndrome, in which CTLs play a pivotal role in the pathogenesis.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine (H.B., G.I., H.F., M.Y., R.H., R.M., K.S., H.N., M.T., Y.T.), Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Nutrition (Y.O.), Kobe Woman's University, Kobe 654-8585; Division of Diabetes and Endocrinology, Department of Medicine (K.T), Jikei University School of Medicine, 105-8461 Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Bando
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Fukuoka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hidaka-Takeno
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Okimura
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology*; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology* / Q000378:metabolism; D011388:Prolactin / Q000172:deficiency; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013972:Thyrotropin / Q000172:deficiency; D050817:Transcription Factor Pit-1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone; D011388:Prolactin; D013972:Thyrotropin