Cutting edge: the Idd3 genetic interval determines regulatory T cell function through CD11b+CD11c- APC.
The Idd3 genetic interval confers protection against multiple autoimmune diseases, including type 1 diabetes and experimental autoimmune encephalomyelitis. The favored candidate gene in this interval is Il2, which is polymorphic between susceptible and resistant strains of mice. IL-2 regulates the growth/death of effector T cells as well as the generation/maintenance of regulatory T cells (Tregs), and recent studies have shown that NOD.Idd3 Tregs are more suppressive than their NOD counterparts. We have further dissected the mechanisms underlying the differential suppression by NOD and NODxIdd3 Tregs and find that it is determined by CD11b(+)CD11c(-) APCs. Thus, contrary to what might be expected, our data suggest that the differential suppressive activity of NOD and NODxIdd3 Tregs is not due to an effect of the Idd3 genetic interval on T cells but rather is due to differences in the APC compartment.
Anderson
Ana C
AC
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. aanderson@rics.bwh.harvard.edu
Chandwaskar
Rucha
R
Lee
David H
DH
Kuchroo
Vijay K
VK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D040641:Quantitative Trait Loci / Q000276:immunology*; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D039481:CD11b Antigen; D039521:CD11c Antigen; D007376:Interleukin-2