gamma delta T cells as mediators of mucosal tolerance: the autoimmune diabetes model

Citation
A. Hanninen et Lc. Harrison, gamma delta T cells as mediators of mucosal tolerance: the autoimmune diabetes model, IMMUNOL REV, 173, 2000, pp. 109-119
Citations number
79
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Immunology
Journal title
IMMUNOLOGICAL REVIEWS
ISSN journal
0105-2896 → ACNP
Volume
173
Year of publication
2000
Pages
109 - 119
Database
ISI
SICI code
0105-2896(200002)173:<109:GDTCAM>2.0.ZU;2-O
Abstract
Mucosal delivery of soluble antigen induces systemic tolerance and has been applied to the prevention of autoimmune diseases. We have studied mucosal tolerance in autoimmune diabetes using the non-obese diabetic mouse model. Treatment of prediabetic mice with the pancreatic islet autoantigen insulin , by aerosol or intranasal delivery, reduces the incidence of diabetes and is associated with induction of CD8 (alpha alpha) gamma delta T cells, smal l numbers of which prevent adoptive transfer of diabetes. We examine the ev idence for gamma delta T cells in mucosal tolerance and discuss possible me chanisms underlying the induction and action of insulin-induced CD8 gamma d elta regulatory T cells. CD8 gamma delta cells constitute the most abundant subpopulation of intraepithelial lymphocytes (IELs), the major lymphoid ce ll compartment and first line of cellular immune defence in the mucosa. Ind uction of regulatory CD8 gamma delta T cells requires conformationally inta ct but not biologically active insulin. In contrast, intranasal (pro)insuli n peptide, or oral insulin which is degraded in the gut, induces CD4 regula tory cells. Regulatory gamma delta T cells secrete interleukin-10 in pancre atic lymph nodes, which could account for the antidiabetic and bystander su ppressor effect of naso-respiratory insulin. The physiological role of gamm a delta IELs in maintaining peripheral self-tolerance deserves further stud y.