Antiproliferative factor against the human glioblastoma cell line T98G identified in culture supernatants of CD4 + cells from patients with HTLV-I-associated myelopathy

Abstract

We investigated culture supernatants of peripheral blood mononuclear cells (MNC) derived from patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) for antiproliferative activity against the human glioblastoma cell line T98G. When T98G cells were cultured with condition medium containing culture supernatants of MNC from patients with HAM, the proliferation of T98G cells was significantly suppressed, compared with that of supernatants from HTLV-I seropositive carriers or seronegative controls. To clarify which population of MNC produced the antiproliferative humoral factor for T98G cells, we separated MNC into macrophage-depleted or B cell depleted populations, and further to both CD4 + and CD8 + T cells by using the panning method or plastic adherence. These studies demonstrated that the antiproliferative activity was mediated by a humoral factor produced by T cells, specifically CD4 + cells. This activity was blocked by a neutralizing monoclonal antibody against interferon-γ (IFN-γ). Moreover, IFN-γ levels were elevated in the culture supernatants of CD4 + cells from HAM patients. Thus, the antiproliferative activity against T98G cells is mainly due to IFN-γ derived from CD4 + cells of patients with HAM.