| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* The Jackson Laboratory, Bar Harbor, ME 04609;
School of Biosciences, University of Birmingham, Birmingham, United Kingdom;
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and
Diabetes Research Laboratories, Massachusetts General Hospital, Cambridge, MA 02138
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 
-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, -galactosylceramide pretreatment did not protect the CD38-deficient stock from T1D induced by an adoptively transferred pancreatic 
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants DK46266 (to D.V.S.), DK51090 (to D.V.S.), DK36175 (to E.H.L.), DK27722 (to E.H.L.), AI45889 (to S.A.P.), and AI51392 (to S.A.P.); Cancer Center Support Grant CA34196; as well as by grants from the Juvenile Diabetes Research Foundation (to D.V.S. and S.B.W.) and Riva Foundation (to S.B.W.). Y.-G.C. was supported by a Postdoctoral Fellowship from Juvenile Diabetes Research Foundation. G.S.B. was supported as a Lister-Jenner Research Fellow and by the Medical Research Council and Wellcome Trust.
2 Address correspondence and reprint requests to Dr. David V. Serreze, Senior Staff Scientist, The Jackson Laboratory, Bar Harbor, ME 04609. E-mail address: dvs{at}jax.org
3 Abbreviations used in this paper: T1D, type 1 diabetes; iNKT, invariant NK T; DN, double negative; -GalCer, -galactosylceramide; DC, dendritic cell; PLN, pancreatic lymph node; Treg, regulatory T cell; 2m, 2-microglobulin; ART, ADP-ribosyltransferase; TCM, tissue culture medium; CM, conditioned medium; WT, wild type; MLN, mesenteric LN; PI, propidium iodide; BM, bone marrow; KO, knockout.
This article has been cited by other articles:
|
|
 |
|
  F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wu and L. V. Kaer Role of NKT Cells in the Digestive System. II. NKT cells and diabetes Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G919 - G922. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
