High potential to tumor necrosis factor alpha (TNF-alpha) production of thyroid infiltrating T lymphocytes in Hashimoto's thyroiditis: a peculiar feature of destructive thyroid autoimmunity.
T lymphocytes present in thyroid infiltrates of 6 patients with Hashimoto's thyroiditis (HT) and of 4 patients with Graves' disease (GD) were analyzed at clonal level and their profiles of mitogen-induced lymphokine secretion were characterized. Production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma) was measured in culture supernatants of a total number of 332 T cell clones (TCC) from HT, of 269 TCC from GD infiltrates and of 266 control TCC derived from normal lymphoid tissues. No significant difference was found in the ability to produce IL-2 between TCC from HT or GD infiltrates and control TCC. The proportion of HT- or GD-derived TCC able to produce IL-4 was extremely low (4 and 5%, respectively) in comparison with controls (19%). In contrast, the proportion of interferon-gamma (IFN-gamma)-producing (IFN-P) TCC derived from either HT (87%) or GD (80%) infiltrates was much higher (p less than 0.0005) than that found in controls (59%). In addition, most of IFN-P TCC from either HT or GD usually released higher amounts (p less than 0.002) of IFN-gamma than did control clones. No significant difference was found between GD infiltrates and controls in the proportions of TCC able to secrete TNF-alpha (39% and 47%, respectively), whereas the proportion of TNF-alpha-producing (TNF-P) TCC derived from HT (78%) was significantly higher (p less than 0.0001). In addition, most of both CD8 and CD4 TCC from HT released higher amounts of TNF-alpha than did TNF-P clones from controls or GD. These data suggest that T cells present in autoimmune thyroid infiltrates share a number of functions, such as high production of IFN-gamma, but differ with regard to their ability to secrete TNF-alpha, which is peculiar of most T cells present in the thyroid of HT patients.
Del Prete
G F
GF
Allergology and Clinical Immunology, University of Florence, Italy.
Tiri
A
A
De Carli
M
M
Mariotti
S
S
Pinchera
A
A
Chretien
I
I
Romagnani
S
S
Ricci
M
M
D000945:Antigens, Differentiation, T-Lymphocyte; D015551:Autoimmunity; D015704:CD4 Antigens; D016827:CD8 Antigens; D002999:Clone Cells / Q000276:immunology; D006111:Graves Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma