Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes.
Web of Science
AuthorHarrison, LC; Dempsey-Collier, M; Kramer, DR; Takahashi, K
Source TitleJournal of Experimental Medicine
PublisherRockefeller University Press
University of Melbourne Author/sHarrison, Leonard
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsHarrison, L. C., Dempsey-Collier, M., Kramer, D. R. & Takahashi, K. (1996). Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes.. J Exp Med, 184 (6), pp.2167-2174. https://doi.org/10.1084/jem.184.6.2167.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196363
Cellular immune hyporesponsiveness can be induced by the presentation of soluble protein antigens to mucosal surfaces. Most studies of mucosa-mediated tolerance have used the oral route of antigen delivery and few have examined autoantigens in natural models of autoimmune disease. Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulin-dependent diabetes mellitus (IDDM). When we administered insulin aerosol to NOD mice after the onset of subclinical disease, pancreatic islet pathology and diabetes incidence were both significantly reduced. Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9-23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 gamma delta T cells. These findings reveal a novel mechanism for suppressing cell-mediated autoimmune disease. Induction of regulatory CD8 gamma delta T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM.
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