Normalization of elevated CD4(-)/CD8(-) (double-negative) T cells after thymectomy parallels clinical remission in myasthenia gravis associated with thymic hyperplasia but not thymoma

T-cell-dependent B-cell help is likely to be of major importance in the pat hogenesis of myasthenia gravis, but mechanisms provoking a pathological ant i-acetylcholine receptor (AChR) response are poorly understood. We report o n the dysregulation of recently identified CD4(-)/CD8(-) (double-negative) T cells (DN T cells), which have been shown to participate in immunoregulat ion and antibody augmentation. Compared with healthy controls, significantl y increased frequencies of DN T cells were found in the blood of myasthenia gravis patients with lymphofollicular hyperplasia. After thymectomy, howev er, normalization in the number of these cells was seen in parallel with cl inical improvement and reduction in anti-AChR antibody titers, The effect o f thymectomy was observed irrespective of adjuvant treatment and held true for up to 4 years of follow-up. In marked contrast, frequencies similar to control values were found in myasthenia gravis patients with thymoma, with thymectomy having no further reducing effect. These data indicate that CD4( -)/CD8(-) T cells not only participate in the pathogenesis of myasthenia gr avis but also correlate with disease activity and histological findings.