Increased production of B-cell growth factor by T lymphocytes in Graves' thyroid: possible role of CD4+ CD29+ cells.

The possible role of B-cell growth factor (BCGF) in the abnormal activation of B cells in Graves' disease was investigated by measuring the production of BCGF by, and analyzing lymphocyte subsets of, peripheral blood cells and thyroid infiltrates from 10 patients with Graves' disease and peripheral blood cells from 9 healthy controls. Medium from peripheral blood and intrathyroidal T cells cultured in the absence or presence of phytohemagglutinin (PHA) was subjected to a bioassay with a cell line, KS-3.F10, responsive only to BCGF. The percentages of activated (DR+CD4+ and DR+CD8+) T cells in the thyroid of Graves' patients were significantly higher than those in the peripheral blood of patients or controls, whereas the percentage of naive (CD4+CD45RA+) T cells was lower. The percentage of B (CD20+) cells in peripheral blood was increased in patients compared with controls. BCGF production by T cells from the thyroid or peripheral blood of Graves' patients, in the absence or presence of PHA, was significantly greater than that by peripheral T cells from healthy controls. PHA-stimulated BCGF production by peripheral T cells of Graves' patients showed a significant negative correlation with the percentage of DR+CD8+ cells in peripheral blood, whereas spontaneous and PHA-stimulated BCGF production by intrathyroidal T cells from Graves' patients showed a positive correlation with the serum concentrations of triiodothyronine (T3) or thyroxine (T4). The different distributions of CD4+ T-cell subsets between thyroid and peripheral blood suggest an important role for intrathyroidal helper/suppressor-inducer (CD4+CD29+) cells in the increased production of BCGF and consequent exacerbation of autoimmunity in Graves' disease.