Mature, long-lived CD4(+) and CD8(+) T cells are generated by the thymoma in myasthenia gravis

Antibodies to muscle acetylcholine receptors, to other muscle antigens, and to some cytokines are found in the majority of patients with thymic tumors (thymomas) and myasthenia gravis (MG), The role of the tumor in initiating autoimmunity, however, is unclear; in particular, it is not known whether the thymoma exports mature and long-lived T cells, which could provide help for antibody production in the periphery. Here, we quantified recently exp orted thymic T cells using the approach of measuring episomal DNA fragments [T-cell receptor excision circles (TRECs)], generated by T-cell receptor g ene rearrangement, Compared to values in healthy individuals (n = 10) or in patients with late-onset MG (n = 8), TREC levels were significantly raised in both the CD4(+) and CD8(+) peripheral blood compartments of patients wi th thymoma and MG (n = 14, p = 0.002 and p = 0.0004 compared to healthy con trols) but only in the CD8+ compartment of the three patients with thymoma without MG (p = 0.4 and p = 0.01 for CD4(+) and CD8(+)). TREC levels decrea sed following thymectomy to values similar to controls but were substantial ly raised in patients who had developed tumor recurrence (n = 6, p = 0.04 a nd p = 0.02 for CD4(+) and CD8(+))(3) this was associated with increased an tibodies to interferon-alpha and interleukin-12 in the one case studied ser ially, Collectively, these results support the hypothesis that the neoplast ic thymoma tissue itself can generate and export mature, long-lived T cells and that these T cells reflect the thymic pathology and are likely to be r elated to the associated autoimmune diseases. The results also provide a ne w approach for early diagnosis of thymoma recurrence.