The Biophysical Context of Interleukin-15 Presentation: Strategies for Biomimetic Cytokine Delivery [electronic resource].

9781321941227

1 online resource (163 p.)

Access is available to the Yale community.

The complex function of the immune system necessitates a sophisticated and well-regulated system of control. Cytokines are the proteins that facilitate communication between immune cells, and are major players in the communications network that directs immune responses. The cytokine interleukin-15 is a valuable target for therapeutic manipulation, and is understood to play a key role in directing and regulating innate and adaptive immune control. Although the function of interleukin-15 is intimately connected with its biophysical mode of presentation, the impact of the biophysical context of cytokine action remains incompletely understood. We used engineered nanosystems to modulate the biophysical arrangement of interleukin-15 ligands at the nanoscale, delivering this cytokine on nanoparticles in a multivalent, nanoclustered form. We characterized the effects of this system on NK cells and CD8+ T cells, two of the primary targets of IL-15 modulation. We demonstrated novel effects of nanoclustered IL-15 in NK cells, showing stronger activation and enhanced interactions due to the multivalent nature of the system. We also found that nanoclustered IL-15 was able to enhance the antigen-specific activation of CD8+ T cells by transferring IL-15 to the surface of antigen-presenting cells. Our results demonstrate that the action of IL-15 can be biophysically regulated through its spatial arrangement. These results provide new insights into the design of IL-15-based therapies for immunomodulation.

Books / Online / Dissertations & Theses

English

April 12, 2016

Thesis (Ph.D.)--Yale University, 2015.

Yale University.