Interleukin-4 enhances the in vitro precursor cell recruitment for tumor-specific T lymphocytes in patients with glioblastoma

Previously the authors showed that interleukin-4 (IL-4), used in combination with IL-2, increases the reduced proliferation rate of T cells of glioblastomabearing patients after in vitro autologous immunization. In this report, they sought to determine whether this effect is caused by a direct mitogenic effect of IL-4, or rather by an indirect effect through an increased expression of the IL-2 receptor subunits or an enhanced recruitment of responsive cells. Flow cytometric analysis confined that the IL-2 receptor subunits are less expressed on circulating T cells from patients with glioblastoma than on those from healthy donors. Because no significant modification of the expression of the p55 and p75 subunits of the IL-2 receptor is observed in cultures treated with both IL-2 and IL-4, the reported enhanced proliferation rate cannot be attributed to an increased level of IL-2 receptor expression. Limiting dilution assays, using autologous target cell immunization, show that treatment with both cytokines (IL-2 plus IL-4) significantly increases the number of recruitable precursor cells without affecting their proliferation rate. These results indicate that IL-4 facilitates an immune response against the autologous tumor cells in glioblastoma-bearing patients by increasing the recruitable precursor T-cell frequency.