Summary
Interleukin‐7 (IL‐7) is produced by bone marrow and lymphoid stromal cells and is involved in the synthesis, survival and homeostasis of T cells. These attributes are the basis for current strategies to utilize IL‐7 as an immune modulator for several clinical conditions to replenish depleted T‐cell numbers. Because we had previously determined that IL‐7 can induce potent human immunodeficiency virus replication in the otherwise non‐permissive CD4+ naïve T‐cell compartment, we evaluated here the impact of IL‐7 on the phenotype and functional potential of naïve CD4+ T cells in an attempt to understand the mechanism of this induction. We demonstrate that IL‐7 mediated the up‐regulation of CD25, CD95 and human leucocyte antigen‐DR, while it did not alter the expression of CD45RO, CD69, CD40, or CD154. Examination of the cytokine profile of IL‐7‐treated naïve T cells using a Type1/Type2 Proteome Array indicated a remarkable IL‐7‐mediated induction of interferon‐γ production, while the other cytokines evaluated (IL‐2, IL‐12, tumour necrosis factor‐α, IL‐4, IL‐5, IL‐10 and IL‐13) were not affected. Intracellular staining of IL‐7‐treated naïve T cells for interferon‐γ verified the Proteome data. IL‐7 did not induce cell cycle proliferation of naïve CD4+ T cells, as evaluated by 7‐AAD/pyronin immunostaining and carboxyfluorescein diacetate succinimidyl ester dye tracking. IL‐7 treatment of naïve CD4+ T cells induced their ability to prime monocytes, as was indicated by induction of CD80 and CD86 expression on monocytes cocultured with IL‐7‐treated naïve CD4+ T cells. Collectively, these data indicate that IL‐7 signalling is sufficient to phenotypically and functionally prime human CD4+ naïve T cells independent of antigen stimulation.