title: CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice.
abstract: T cell-mediated autoimmune type-1 diabetes (T1D) in NOD mice partly results from this strain's numerical and functional defects in invariant NK T (iNKT) cells. T1D is inhibited in NOD mice treated with the iNKT cell superagonist alpha-galactosylceramide through a process involving enhanced accumulation of immunotolerogenic dendritic cells in pancreatic lymph nodes. Conversely, T1D is accelerated in NOD mice lacking CD38 molecules that play a role in dendritic cell migration to inflamed tissues. Unlike in standard NOD mice, alpha-galactosylceramide pretreatment did not protect the CD38-deficient stock from T1D induced by an adoptively transferred pancreatic beta cell-autoreactive CD8 T cell clone (AI4). We found that in the absence of CD38, ADP-ribosyltransferase 2 preferentially activates apoptotic deletion of peripheral iNKT cells, especially the CD4+ subset. Therefore, this study documents a previously unrecognized role for CD38 in maintaining survival of an iNKT cell subset that preferentially contributes to the maintenance of immunological tolerance.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Yi-Guang
authors.initials: YG
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Osborne
authors.forename: Harold D
authors.initials: HD
authors.lastname: Chapman
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Edward H
authors.initials: EH
authors.lastname: Leiter
authors.forename: S Brian
authors.initials: SB
authors.lastname: Wilson
authors.forename: David V
authors.initials: DV
authors.lastname: Serreze
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD
chemical_list: D036002:ADP Ribose Transferases; D051997:ADP-ribosyl Cyclase 1