ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY AGAINST HUMAN-EYE MUSCLE-CELLS AND ORBITAL FIBROBLASTS IN GRAVES OPHTHALMOPATHY - ROLES OF CLASS-II MHC ANTIGEN EXPRESSION AND GAMMA-INTERFERON ACTION ON EFFECTOR AND TARGET-CELLS

Google Scholar
  • 1 December 1987
    • journal article
    • research article
    • Vol. 70  (3) , 593-603
Abstract
We have studied the significance of antibody dependent cell-mediated cytotoxicity (ADCC) against human orbital fibroblasts (OF) and eye muscle (EM) cells in the pathogenesis of the orbital autoimmune reactions of Graves'' ophthalmopathy (GO). Possible roles of Class II MHC antigen expression on the surface of orbital target cells and of gamma-interferon (.gamma.-IFN) modulation of ADCC were also studied. Both OF and EM expressed HLA-DR antigen when stimulated with .gamma.-IFN and phytohemagglutinin, but not spontaneously, and not by thyroid stimulating hormone or .alpha.-IFN. Intrathyroidal T cells from a patient with GO induced greater DR expression on both OF and EM cells than equal numbers of her peripheral blood T cells. .gamma.-IFN treated EM and OF were more susceptible to lysis in ADCC assays than untreated targets. .gamma.-IFN also enhanced lysis in ADCC assays by an effect on the killer cell population. On the other hand treatment with .alpha.-IFN, which is a potent inducer of Class I antigen expression, did not affect the susceptibility of target cells to lysis in ADCC. When sera from patients with GO were tested in ADCC, tests were positive (% specific lysis > mean + 2 s.d. for normals) in 10 of 20 patients with EM cells, but in only two of 25 with OF. The degree of killing of EM cells was significantly positively correlated to that of abdominal skeletal muscle cells and, to a lesser degree, normal thyroid cells, but not OF. In sera showing killing of EM cells and OF, ADCC activity against EM cells was absorbed by preincubation with EM and orbital connective tissue membranes but not thyroglobulin and, conversely, lysis of THY cells was absorbed by preincubation of positive sera on monolayers of THY and EM cells and OF, but not vasular endothelial (VE) cells. Finally, killing of 51Cr labelled EM cells was inhibited by addition of unlabelled (''cold'') thyroid cells, EM cells, and OF, but not VE cells.