Lysis of human glial cells by major histocompatibility complex-unrestricted CD4+ cytotoxic lymphocytes

We have investigated lysis of cultured human glial cells by non-major histocompatibility complex (MHC)-restricted or 'promiscuous' CD(4+)-T lymphocytes, activated either under relatively long-term limiting dilution culture conditions in the presence of phytohemagglutinin (PHA) and interleukin (IL)-2, or under short-term PHA-activated bulk culture conditions. Specific effector:target cell ratio-dependent lysis of oligodendrocytes (OGCs) by CD4+ T lymphocytes, generated under both of the above conditions, was observed in an 18-h 51Cr-release assay, but not in a 5-h assay. The extent of CD4 T-cell-mediated OGC lysis was less than for the tumor necrosis factor (TNF)-alpha-sensitive cell line U937, but greater than for TNF-resistant cell lines (K562, EL4). The effect could not be reproduced by T-cell culture supernatants or by high concentrations of recombinant TNF-alpha or beta. Anti-TNF-alpha antibody did not inhibit CD4-mediated lysis of OGC or U937 cells, but did inhibit U937 lysis induced by recombinant TNF-alpha, added in amounts exceeding those secreted by CD4 T cells. Human astrocytes and microglia were also susceptible to CD4+ T-cell-mediated lysis. Our results suggest that non-antigen non-MHC-restricted CD4+ T-cell-mediated injury of human glial cells can occur and may be dependent or enhanced by effector:target cell contact.