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IL-7 decreases IL-7 receptor (CD127) expression and induces the shedding of CD127 by human CD8+ T cells

2007; Oxford University Press; Volume: 19; Issue: 12 Linguagem: Inglês

10.1093/intimm/dxm102

1460-2377

Agatha Vranjkovic, Angela M. Crawley, Katrina Gee, Ashok Kumar, Jonathan B. Angel,

HIV Research and Treatment

IL-7 receptor α (CD127) signaling is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Fewer CD8+ T cells from HIV-infected patients express CD127 compared with healthy individuals, suggesting that specific host and/or viral factors regulate IL-7 receptor expression. Factors relevant to HIV infection that could potentially decrease CD127 expression on human CD8+ T cells and the mechanisms by which this occurs were therefore evaluated. IL-7, but not HIV gp120, IL-1-β, IL-6, IL-10, IL-13, transforming growth factor-β or tumor necrosis factor-α, reduced CD127-surface expression and did so without altering CD127 mRNA expression. Furthermore, IL-7 did not increase the amount of cytoplasmic CD127 in CD8+ T cells. Interestingly, IL-7 induced the shedding of CD127 from CD8+ T cells, suggesting a mechanism that may contribute to the increased concentration of CD127 in the plasma of HIV+ individuals, a novel finding reported here. Naive CD8+ T cells are more sensitive to IL-7 that mediated the down-regulation of CD127, suggesting that these effects may have particular significance early in T-cell life cycle. Since CD127 down-regulation may be an important contributor to HIV-associated T-cell dysfunction, determining the mechanism thereof may prove to be of considerable significance.