Disturbances in the Peripheral T-Cell Repertoire of Patients with Motor Neuron Disease: High Levels of Activation and Indirect Evidence of Superantigen

Our data on peripheral blood T cells from Motor neuron disease (MND) patients indicate major immunological disturbances linked to this disease. Both CD4+ and CD8+ T-cell subsets display an increased fraction of cells showing activation markers compared to controls, indicating an unusually high level of activity in both populations. Likewise, an increased number of T-cell expansions were noted in MND patients compared to controls, most dramatically observed in the CD4+ T-cell subset, where 5/144 T-cell V genes analyzed in eight subjects turned out to be expanded in the peripheral blood. In the CD8+ T-cell subset, four out of eight MND patients had peripheral BV gene expansions, 9/144 V genes analyzed. However, the most interesting result was the observation that in three out eight MND patients, expansions concerning the same BV gene were present in both CD4+ and CD8+ subsets (BV8S1 in two and BV12S1 in one patient). Parallel expansions of BV-gene restricted populations in both CD4+ and CD8+ subsets in the same individual, in an major histocompatibility complex (MHC)-unrestricted manner, are normally limited to situations where superantigens are involved. No known superantigen has to date been described with the capacity to simultaneously stimulate both BV8S1 and BV12S1, suggesting that the postulated 'MND-associated' superantigen is a hitherto undefined molecule.