Low-dose IL-2 selectively activates subsets of CD4+ Tregs and NK cells.

By M. Hirakawa, T. R. Matos, Hongye Liu, J. Koreth, Haesook T. Kim, Nicole E. Paul, K. Murase, J. Whangbo, Ana C Alho, S. Nikiforow and 9 more. 2016

137 citations recorded by the source corpus.

CD4+ regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood. Using mass cytometry, we demonstrate that low concentrations of IL-2 selectively induce STAT5 phosphorylation in Helios+ CD4Tregs and CD56brightCD16- NK cells in vitro. Preferential activation and expansion of Helios+ CD4Tregs and CD56brightCD16- NK cells was also demonstrated in patients with chronic GVHD receiving low-dose IL-2. With prolonged IL-2 treatment for 48 weeks, phenotypic changes were also observed in Helios- CD4Tregs. The effects of low-dose IL-2 therapy on conventional CD4+ T cells and CD8+ T cells were limited to increased expression of PD-1 on effector memory T cells. These studies reveal the selective effects of low-dose IL-2 therapy on Helios+ CD4Tregs and CD56bright NK cells that constitutively express high-affinity IL-2 receptors as well as the indirect effects of prolonged exposure to low concentrations of IL-2 in vivo.

Subfields: Hematology, Immunology

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In Immunology

1. Josef Spidlen
2. Richard L. Halpert
3. Chris Ciccolella
4. R. Anno
5. J. Snyder-Cappione
6. Anna C. Belkina

Citations in the corpus

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