This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sensitivity to dietary gluten is a prominent feature of celiac disease (CD), a major histocompatibility class two allele DQ2/8-linked chronic inflammatory condition of the small intestine. We recently established the non-human primate model of gluten sensitivity where several of the key clinical, histopathological and serological characteristics of the above condition were described ?in association with altered physiological function of the small intestine. In this study, we extended these observations by focusing on the cellular origin and plasma levels of tissue tranglutaminase (TG2)-specific autoantibodies in gluten sensitive rhesus macaques (Macaca mulatta). We also measured the anti-gliadin antibodies in plasma, interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) positive T cells in duodenal biopsies obtained from animals with/without gluten sensitivity. A selected group of four gluten-sensitive and two control macaques were placed on a gluten-free diet for a period of two months, followed by challenge with gluten-containing diet. Administration of a gluten-free diet to gluten sensitive macaques caused remission, associated with disappearance of TG2+IgG+ double positive B cells and replacement of CD4+IFN-gamma+ T cells with CD4+IL10+ T cells in duodenum, and disappearance of TG2+IgA+ B cells from the dermis of one gluten sensitive macaque. Reintroduction of dietary gluten caused immunological relapse and reappearance of the clinical symptoms of diarrhea and/or dermatitis. Above dietary change had no effect on age-matched controls. To our knowledge, this is the first report to illustrate the presence and source of TG2-specific autoantibodies in any animal model of gluten sensitivity. Moreover, the similarity of tissue distribution of TG2-specific, autoantibody secreting B cells between the gluten sensitive rhesus macaques and celiac patients highlights the potential of this animal model in further studies with novel therapy approaches as well as in studies to further elucidate the questions in respect to gliadin-specific immune response ?the mechanism of which is incompletely understood.
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