Activated suppressor cell function in multiple sclerosis — clinical correlations☆

Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis.

“…A similar effect of anti-IFN-y monoclonal antibody was observed in the mouse model of experimental autoimmune uveoretinitis (46 (13)(14)(15)(16)(17). Antel et al reported that this defect primarily resides in the CD8+ population and found a decrease in suppression mediated by CD8+ T cell lines from patients with progressive MS (14).…”

“…A number of antigen nonspecific immune abnormalities have been described in MS, particularly in patients with the chronic progressive form of the disease. These abnormalities include a decrease of Concanavalin A, anti-CD3, and AMLR induced T cell-mediated suppression (13)(14)(15)(16)(17), and an impaired autologous mixed lymphocyte reaction (AMLR) (18,19).…”

Application of Lymphocyte Immunophenotyping in Selected Diseases

“…In an earlier study, Rose et al [36] using two color analysis of MS lymphocytes, demonstrated a selective reduction of this same lymphocyte popula tion in MS patients with active disease. Fi nally, functional suppressor T cell defects have been confirmed by several investigators [35,37], It is not known whether or not these common phenotypic and functional cell changes in MS are part of the underlying pathogenesis or a result of the disease it self.…”

Cell-Mediated Immune Functions in Multiple Sclerosis

“…After 3 days cells are washed and their DNA synthesis is blocked by mitomycin C. Irradiation should be avoided as it abrogates suppression [Siegal and Siegal, 1977], Cells are then added to freshly isolated responder cells which are stimulated with Con A and suppression is measured as a ratio between the amount of Con-A-induced DNA synthesis in the re sponder cells plus Con-A-stimulated sup pressor cells versus the amount of DNA syn thesized by responder cells + unstimulated cells. Multiple groups have consistently dem onstrated a reduction in suppression during active clinical disease Antel et al, 1978Antel et al, , 1979Antel et al, , 1986Neigh bor and Bloom, 1979;Sheramata et al, 1982;Haahr et al, 1983;Tjernlund et al, 1984;Gonzalez et al, 1979;Oger et al, 1985;O'Gorman et al, 1987]. Additionally, Con-A-induced suppression appears to fluc tuate with changes in clinical disease activity falling prior to an attack and rising to levels above those seen in normal controls during the remitting phase of the disease [Antel et al, , 1979, Difficulties have arisen in determining the exact mechanism of Con-Ainduced suppression although a recent re port suggested the functional suppressor de fect in MS patients is in the OKT8 cell subset [Antel et al, 1986].…”

“…Multiple groups have consistently dem onstrated a reduction in suppression during active clinical disease Antel et al, 1978Antel et al, , 1979Antel et al, , 1986Neigh bor and Bloom, 1979;Sheramata et al, 1982;Haahr et al, 1983;Tjernlund et al, 1984;Gonzalez et al, 1979;Oger et al, 1985;O'Gorman et al, 1987]. Additionally, Con-A-induced suppression appears to fluc tuate with changes in clinical disease activity falling prior to an attack and rising to levels above those seen in normal controls during the remitting phase of the disease [Antel et al, , 1979, Difficulties have arisen in determining the exact mechanism of Con-Ainduced suppression although a recent re port suggested the functional suppressor de fect in MS patients is in the OKT8 cell subset [Antel et al, 1986]. Suppressor factors are involved and candidates include interferon gamma and alpha.…”