ABNORMAL T-CELL RECEPTOR-V GENE USAGE IN MYASTHENIA-GRAVIS - PREVALENCE AND CHARACTERIZATION OF EXPANDED T-CELL POPULATIONS

The usage of T cell receptor (TCR) V alpha/V beta chains on cells from 38 patients with myasthenia gravis (MG) was determined by flow cytome try. There was a decreased number of cells expressing V beta 2 in CD8( +) and V beta 3 in CD4(+) cells in patients compared with healthy indi viduals. Abnormal expansions of T cells using particular TCR V alpha/V beta gene products were found in 18/38 patients. A significantly high er usage of V beta 13 was observed but there was no restriction with r egard to other TCR V alpha/V beta. Expanded cells belonging to both CD 4(+) and CD8(+) were present in MG patients while restricted to the CD 8(+) population in healthy individuals. To elucidate the role of the e xpanded populations, we studied characteristics of the expanded and no n-expanded T cells from MG patients who had persistent T cell expansio ns over more than years. The cells were analysed with regard to phenot ype, cytokine secretion, cytokine mRNA expression and reactivity with the autoantigen, the acetylcholine receptor. The characteristics of th e expanded populations in MG clearly differed from those found in heal thy individuals. More cells in the CD4(+) expanded populations express ed HLA-DR and there was also a tendency for higher expression of CD25, CD28 and CD57. The number of cells spontaneously secreting cytokines was higher in the expanded populations. A dominant Th1-type cytokine s ecretion and mRNA expression was noted. Autoantigen-reactive CD3(+) T cells were largely restricted to the expanded populations.