Adherence-mediated T cell activation in multiple sclerosis and other neurological disorders

Peripheral blood T cells were isolated from chronic progressive multiple sclerosis patients using a stepwise protocol of density gradient centrifugation, erythrocyte rosetting and adherent cell depletion, after which T cells were cultured with no added stimulus. These cultures exhibited as much as 10-fold higher 'background' proliferative activity (designated hyperactivity) than similarly prepared cultures from normal healthy control individuals. Hyperactivity was also found with T cell cultures from patients with other neurological disorders, i.e. namely, Guillain-Barré syndrome, acute stroke, myasthenia gravis or seizures. Characterizing the hyperactivity, kinetic studies showed that it was not evident until 6 days and became maximal in 8-10 day cultures; it occurred concomitantly with an increase in activated cells; and it was inhibited by anti-HLA-DR antibody, implicating the role of CD4+ T cells. Taken together, these results suggest that the hyperactivity was the result of in vitro stimulation. In further support of this view, hyperactivity was dependent on the adherence step used in the T cell isolation procedure. Although the T cell stimulus and the mechanism underlying the adherence effect is currently speculative, the hyperactivity appears to be the result of a feature common to the diseases in which it was found. The possible roles of inflammatory events in vivo and an autologous mixed lymphocyte response in vitro are discussed.