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CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice. J Immunol 2006 Sep 01;177(5):2939-47

Date

08/22/2006

Pubmed ID

16920929

DOI

10.4049/jimmunol.177.5.2939

Scopus ID

2-s2.0-33747775837   26 Citations

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.

Author List

Chen YG, Chen J, Osborne MA, Chapman HD, Besra GS, Porcelli SA, Leiter EH, Wilson SB, Serreze DV

Author

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

ADP Ribose Transferases
ADP-ribosyl Cyclase 1
Animals
CD4-Positive T-Lymphocytes
Cell Survival
Cells, Cultured
Diabetes Mellitus
Lymphocyte Activation
Mice
Mice, Inbred NOD