Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent
immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an
injectable, porous
hydrogel to induce a regulatory T cell (Treg) response by delivering a
peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC
peptide from pore-forming
alginate gels in the nonobese diabetic mouse model of
type 1 diabetes: encapsulation in
poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the
alginate polymer. While particle-based delivery leads to
antigen-specific T cells responses in vivo, PLG particles alter the phenotype of the cells infiltrating the
gels. Following gel-based
peptide delivery, transient expansion of endogenous
antigen-specific T cells is observed in the draining lymph nodes.
Antigen-specific T cells accumulate in the
gels, and, strikingly, ≈60% of the
antigen-specific CD4+ T cells in the
gels are Tregs.
Antigen-specific T cells are also enriched in the pancreatic islets, and administration of
peptide-loaded
gels does not accelerate diabetes. This work demonstrates that a noninflammatory
biomaterial system can generate
antigen-specific Tregs in vivo, which may enable the development of new
therapies for the treatment of transplant rejection or
autoimmune diseases.