AUTHOR=Sestak Karol , Dufour Jason P. , Liu David X. , Rout Namita , Alvarez Xavier , Blanchard James , Faldas Anne , Laine David J. , Clarke Adam W. , Doyle Anthony G. 

TITLE=Beneficial Effects of Human Anti-Interleukin-15 Antibody in Gluten-Sensitive Rhesus Macaques with Celiac Disease

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01603

DOI=10.3389/fimmu.2018.01603

ISSN=1664-3224

ABSTRACT=Over-expression of interleukin-15 (IL-15) is linked with immunopathology of several autoimmune disorders including celiac disease. Here we utilized an anti-human IL-15 antibody 04H04 (anti-IL-15) to reverse immunopathogenesis of celiac disease. Anti-IL-15 was administered to 6 gluten-sensitive rhesus macaques with celiac disease characteristics including gluten-sensitive enteropathy, and the following celiac-related metrics were evaluated: morphology (villous height / crypt depth ratio) of small intestine, counts of intestinal intraepithelial lymphocytes, IFN-γ-producing CD8+ and CD4+ T cells, plasma levels of anti-gliadin and anti-intestinal tissue transglutaminase (TG2) IgG antibodies, as well as peripheral effector memory (CD3+CD28-CD95+) T cells. Anti-IL-15 treatment reversed the clinically relevant disease endpoints, intraepithelial lymphocyte counts and villous height / crypt depth ratios within jejunal biopsies to normal levels (P<0.001). Additionally, intestinal CD8+ and CD4+ T cell IFN-γ production was reduced (P<0.05). Extra-intestinally, anti-IL-15 treatment reduced peripheral NK cell counts (P<0.001) but otherwise non-NK peripheral lymphocytes including effector memory T cells and serum blood chemistry were unaffected. Overall, providing the beneficial disease-modulatory and immunomodulatory effects observed, anti-IL-15 treatment might be considered as a novel therapy to normalize intestinal lymphocyte function in celiac disease patients with gluten-sensitive enteropathy.