Activation of immunoregulatory lymphocytes obtained from patients with malignant gliomas

The responsiveness of T cells and their subsets (T-helper cells and T-suppressor cells) obtained from patients with malignant gliomas was evaluated in an effort to further define the mechanism of their impaired host immunocompetence. This study demonstrates that peripheral blood lymphocytes obtained from these patients have impaired responsiveness to a variety of mitogens including phytohemagglutinin, concanavalin A, pokeweed mitogen, and anti-T3 monoclonal antibody. The impaired lymphocyte responsiveness does not result from the inability of these cells to express receptors for a specific mitogen or antibody. The mitogenic responsiveness of purified T cells is markedly reduced when compared to values obtained from control subjects. Therefore, the decreased T cell reactivity of patients with malignant gliomas does not result simply from a diminution in the absolute number of potentially responding lymphocytes. The mitogen reactivity of the T cell subsets, CD4+ helper cells, and CD8+ cytotoxic/suppressor cells was also investigated. These results demonstrate that the responsiveness of the CD4+ T-helper cell subset obtained from these patients is consistently diminished as compared to control values. In contrast, the reactivity of the CD8+ T cell subset was not nearly as dramatically impaired. Thus, these results indicate that the proliferative defect observed in T cells obtained from patients is located predominantly in the T-helper cell subset. Functional deficiencies in this important subpopulation of T lymphocytes may explain, in part, the presence of depressed immune responsiveness in patients with malignant glial tumors.