SINGLE-CELL ANALYSIS OF INTRATHYROIDAL LYMPHOCYTES SHOWS DIFFERENTIALCYTOKINE EXPRESSION IN HASHIMOTOS AND GRAVES-DISEASE

ROURAMIR C CATALFAMO M SOSPEDRA M ALCALDE L PUJOLBORRELL R JARAQUEMADA D

C. Rouramir et al., SINGLE-CELL ANALYSIS OF INTRATHYROIDAL LYMPHOCYTES SHOWS DIFFERENTIALCYTOKINE EXPRESSION IN HASHIMOTOS AND GRAVES-DISEASE, European Journal of Immunology, 27(12), 1997, pp. 3290-3302

41

INGLESE

Article

European Journal of Immunology → ACNP

0014-2980

27

12

1997

3290 - 3302

ISI

0014-2980(1997)27:12<3290:SAOILS>2.0.ZU;2-O

Most human organ-specific autoimmune diseases such as Hashimoto's thyr oiditis (HT) are considered to be Th1 mediated, and a quantitative dom inance of Th1 cells in thyroid infiltrates from both Graves' disease ( GD) and HT affected glands has been reported. However, Th2 dominance w ould be expected in GD, where thyroid hyperfunction induced by stimula ting antibodies predominates over tissue destruction. We have analyzed the interleukin-4 (IL-4), interferon-gamma (IFN-gamma) production by T cells at the single-cell level, both in infiltrating lymphocytes iso lated from digested GD and HT thyroid glands and in derived T cell lin es, by direct intracellular cytokine detection, Results showed a heter ogeneous pattern of cytokine production in bulk GD infiltrates and der ived T cell lines, and a similar pattern was observed in the much larg er HT infiltrates. Both type 1 and type 2 cytokines were simultaneousl y produced by the infiltrating populations, and T cells with both patt erns as well as intermediate patterns similar to Th0 cells could be de tected ex vivo. However, the larger T lymphocytes, presumably activate d and responsible for the autoimmune damage, predominantly produced IL -4 in GD and IFN-gamma in HT. The specificity of the Th2 responses in GD was suggested by the enrichment in IL-4 production after antigen-sp ecific expansion of two oligoclonal T cell lines. These data show that both type 1 and type 2 cytokines are produced in the thyroid glands a ffected by autoimmunity and that the difference between diseases may b e the effect of a functionally dominant population at a given time. Th is in vivo chronically activated antigen-specific population, producin g type 1 or type 2 cytokines locally, may be responsible for the effec t finally leading to one of the disease states.