Cord Blood T Cells Cultured With IL-7 in Addition to IL-2 Exhibit a Higher Degree of Polyfunctionality and Superior Proliferation Potential

Abstract

One disadvantage with umbilical cord blood transplantation is that donor lymphocyte infusion (DLI) for treatment of threatening rejection or relapse of underlying malignant disease is not available. We have previously expanded T cells from the cord blood graft in clinical setting using anti-CD3(+)/CD28(+) paramagnetic beads and interleukin (IL)-2 for possible future DLI. Here we studied the effect of adding clinical-grade IL-7 to the expansion protocol. T cells were positively selected with anti-CD3(+)/CD28(+) paramagnetic beads and cultured in increasing concentrations of IL-2 with and without IL-7 (20 ng/mL). After 7 days of expansion, the T cells were analyzed for proliferative capacity and investigated with flow cytometry and Luminex to determine phenotype, cytokine production, and responsiveness to mitogenic stimulus. Cultures with IL-7 had significantly greater proliferation rate, higher CD4(+)/CD8(+) ratio, a lower percentage of central memory T cells (CD45RO(+)CCR7(+)), and a higher percentage of effector memory T cells (CD45RO(+)CCR7(-)). We assessed the production of IL-2, tumor necrosis factor-, interferon-, and CD107a and found a higher percentage of polyfunctional T cells (positive for 3 to 4 factors) in cells cultured with IL-7. The addition of IL-7 gives a proliferative advantage, also in cultures with a lower dose of IL-2. This could prove advantageous in T-cell culture for adoptive transfer to decrease the risk of apoptosis and other negative effects of cytokine deprivation in vivo. Addition of IL-7 also had an effect on the differentiation status of the cord blood-derived T cells. T cells cultured in IL-7 had more polyfunctional traits, possibly increasing the activity of a putative future umbilical cord blood DLI.