Selective Loss of the Suppressor-Inducer T-Cell Subset in Progressive Multiple Sclerosis

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Abstract
The T4+ lymphocyte population includes a subset that induces suppressor T lymphocytes (T8+ cells) and can be distinguished by dual-color fluorescence analysis with anti-2H4 and anti-T4 monoclonal antibodies. To investigate the possible role of these cells in multiple sclerosis, we used anti-2H4 antibody to characterize peripheral-blood lymphocyte subsets in 63 patients with multiple sclerosis that was progressive, stable, or acute (relapsing–remitting). Twenty-three of 37 patients with progressive multiple sclerosis had a selective decrease in the number and percentage of peripheral-blood T cells that induce suppressor cells (T4+2H4+ cells), whereas only 3 of 16 patients with stable disease and 2 of 10 patients in the midst of an acute attack had a significant decrease. These selective decreases of circulating T4+2H4+ cells occurred in only 1 of 34 patient controls with other neurologic diseases and in 2 of 50 healthy controls (P<0.0001 by Fisher's exact test). The absolute number of T4+2H4+ cells and the percentage of reactivity in the populations studied were 187±28 per cubic millimeter and 8.3±1 percent in patients with progressive multiple sclerosis; 353±60 per cubic millimeter and 14.5±2 percent in patients with stable disease; 368±72 and 14.6±2.1 percent in patients with acute disease; 402±64 and 15.6±2 percent in controls with other neurologic diseases; and 519±44 and 19.7±1 percent in healthy controls. Functional studies using a pokeweed mitogen–driven IgG assay demonstrated a correlation between decreased numbers of T4+2H4+ cells and increased production of IgG in vitro. Family studies showed that the 2H4 antigen was not part of an inherited polymorphic antigenic determinant.