CD38 is required for the peripheral survival of immunotolerogenic CD4 + invariant NK T cells in nonobese diabetic mice

Yi Guang Chen, Jing Chen, Melissa A. Osborne, Harold D. Chapman, Gurdyal S. Besra, Steven A. Porcelli, Edward H. Leiter, S. Brian Wilson, David V. Serreze

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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 α-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, α-galactosylceramide pretreatment did not protect the CD38-deficient stock from T1D induced by an adoptively transferred pancreatic β 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.

Original languageEnglish (US)
Pages (from-to)2939-2947
Number of pages9
JournalJournal of Immunology
Volume177
Issue number5
StatePublished - Sep 1 2006

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Inbred NOD Mouse
Type 1 Diabetes Mellitus
Natural Killer Cells
T-Lymphocytes
Galactosylceramides
Dendritic Cells
ADP Ribose Transferases
T-Lymphocyte Subsets
Cell Movement
Clone Cells
Lymph Nodes
Maintenance

ASJC Scopus subject areas

  • Immunology

Cite this

Chen, Y. G., Chen, J., Osborne, M. A., Chapman, H. D., Besra, G. S., Porcelli, S. A., ... Serreze, D. V. (2006). CD38 is required for the peripheral survival of immunotolerogenic CD4 + invariant NK T cells in nonobese diabetic mice. Journal of Immunology, 177(5), 2939-2947.

CD38 is required for the peripheral survival of immunotolerogenic CD4 + invariant NK T cells in nonobese diabetic mice. / Chen, Yi Guang; Chen, Jing; Osborne, Melissa A.; Chapman, Harold D.; Besra, Gurdyal S.; Porcelli, Steven A.; Leiter, Edward H.; Wilson, S. Brian; Serreze, David V.

In: Journal of Immunology, Vol. 177, No. 5, 01.09.2006, p. 2939-2947.

Research output: Contribution to journalArticle

Chen, YG, Chen, J, Osborne, MA, Chapman, HD, Besra, GS, Porcelli, SA, Leiter, EH, Wilson, SB & Serreze, DV 2006, 'CD38 is required for the peripheral survival of immunotolerogenic CD4 + invariant NK T cells in nonobese diabetic mice', Journal of Immunology, vol. 177, no. 5, pp. 2939-2947.
Chen, Yi Guang ; Chen, Jing ; Osborne, Melissa A. ; Chapman, Harold D. ; Besra, Gurdyal S. ; Porcelli, Steven A. ; Leiter, Edward H. ; Wilson, S. Brian ; Serreze, David V. / CD38 is required for the peripheral survival of immunotolerogenic CD4 + invariant NK T cells in nonobese diabetic mice. In: Journal of Immunology. 2006 ; Vol. 177, No. 5. pp. 2939-2947.
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