Table 1.

Overlap Between Cell Mediated Immune Defects and Regulatory T cell Functions in Patients with Malignant Glioma

CMI Deficits in Patients with Malignant Glioma	Regulatory T cell functions
Concentrated in CD4+ T-cell subset	Concentrated in CD4+ T-cell subset
T-cell IL-2R defects observed	Characterized by CD25 (IL-2Rα) expression and induce IL-2R defects in target cells
T-cells anergic: fail to proliferate and produce IL-2	Anergic. Inhibit T-cell proliferation and IL-2 production
Tumors produce TGF-β and IL-10	TGF-β and IL-10 induce regulatory phenotype in T lymphocytes
Lymphocytes produce TGF-β and IL-10 in response to stimulation, and fail to produce IFN-γ	Induce TGF-β and IL-10 production in surrounding T-cells, and inhibit IFN-γ production.

The well-described CMI defects found in patients with malignant glioma (left column) exhibit significant overlap in phenotype with the more recently described inhibitory properties of CD4⁺CD25⁺FOXP3⁺ Tregs (right column). We found that patients with malignant glioma have elevated proportion of Tregs amidst an overall diminished CD4+T cell compartment and proliferative and cytokine production defects observed in lymphocytes from these patients could be completely restored by removal of Tregs in vitro (373). These studies suggest that Tregs are a major source of potentially reversible immunosuppression in patients with malignant glioma.