A Low Effective Dose of Interleukin-7 Is Sufficient to Maintain Cord Blood T Cells Alive without Potentiating Allo-Immune Responses

• We evaluated the survival of cord blood T cells from 34 cord blood units and observed that freshly collected cord blood T cells left unstimulated lost their viability very quickly after incubation compared to their adult counterpart.
• This viability of cord blood T cells was negatively correlated to infant birth weight (Spearman's ρ = .376; P = .031) and positively correlated to venous cord blood pH.
• At 100 pg/mL, IL-7 was sufficient to maintain the viability of cord blood T cells.
• At 100 pg/mL, IL-7 did not lead to any significant enhancement of the alloreactive response of cord blood T cells.
• This suggests that low-dose IL-7 is sufficient to sustain the viability of infused cord blood T cells without potentiating their alloreactivity.

Slow reconstitution of T cell immunity remains a critical issue after umbilical cord blood (CB) transplantation. Although this may be a consequence of the low cell dose, it may also reflect the propensity of naïve T cells, which predominate in CB, to undergo apoptotic cell death. Exogenous interleukin 7 (IL-7) can prevent apoptosis of naïve T cells, but at high concentrations, IL-7 may also expand alloreactive T cells, thereby aggravating the risk of graft-versus-host disease. We evaluated the survival of CB T cells from 34 healthy full-term pregnancies, and we found wide interdonor variation, from 17.4% to 79.7%, of CB T cells that were still alive after being rested for 4 days in culture medium without cytokine supplementation. The viability of CB T cells was negatively correlated to infant birth weight (Spearman's ρ = .376; P = .031) and positively correlated to venous CB pH (ρ = .397; P = .027); both associations were confirmed by multivariate analysis (P = .023 and P = .005, respectively). A low supplemental concentration (100 pg/mL) of recombinant human IL-7 was sufficient to maintain the viability of cryopreserved/thawed CB T cells, with most (>80%) cells remaining in a quiescent state and without significant changes in their CD4/CD8 ratio and the proportion of CD4+ CD31+ PTK7+ recent thymic emigrants. IL-7 at 100 pg/mL did not lead to any significant enhancement of the alloreactive response of CB T cells, as evaluated by proliferation rates (thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester dilution) and interferon-gamma production (ELISPOT). This effective concentration of IL-7 is far lower than that obtained in vivo after pharmacological administration of the cytokine. This study suggests that administration of lower doses of recombinant human IL-7 than used in previous clinical trials may be sufficient to sustain the viability of infused CB T cells and, thus, help to accelerate naïve T cell reconstitution without potentiating their alloreactivity.