Interleukin 2-activated killer cells do not mediate autologous thyrocyte lysis in autoimmune thyroid disease in vitro.
Because of interest in IL-2, and IL-2-activated killer cell-induced hypothyroidism in humans, we attempted to study an in vitro system that might prove to illuminate this disorder. We have thus studied interleukin 2 (IL-2--0, 12.5, 25, or 50 U/mL) activated killer cell-mediated autologous thyrocyte lysis, as well as cytotoxic activity in IL-2-stimulated mononuclear cell supernatants in 7 patients with autoimmune thyroid disease (2 Graves' disease and 5 Hashimoto's thyroiditis) using the 51Cr release assay. Controls included 14 patients with nonautoimmune thyroid disease (3 nontoxic goiter, 8 follicular thyroid adenoma, 2 papillary thyroid carcinoma, and 1 medullary carcinoma of the thyroid). Soluble IL-2 receptor (sIL-2R) in supernatants of peripheral mononuclear cells stimulated by IL-2 from these patients also was measured. Whereas in the control preparations, IL-2-activated killer cell activity was increased in a dose-dependent fashion relative to the IL-2 concentration, as well as to the effector cell/target cell ratio, in preparations from patients with autoimmune thyroid disease, this activity was not elevated as the IL-2 concentration was increased. The susceptibility of thyrocytes to the lytic effect of IL-2-activated killer cells was higher in controls than that in autoimmune thyroid disease (at concentrations of IL-2 of 0, 12.5, 25, and 50 U/mL) (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Matsubayashi
S
S
Endocrinology Research Laboratory, Wellesley Hospital, University of Toronto, Canada.
Akasu
F
F
Kasuga
Y
Y
Jamieson
C
C
Volpé
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D016923:Cell Death / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013961:Thyroid Gland / Q000473:pathology* / Q000648:ultrastructure; D013967:Thyroiditis, Autoimmune / Q000473:pathology* / Q000503:physiopathology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2