Send to:

Choose Destination
See comment in PubMed Commons below
Ann N Y Acad Sci. 2008 Dec;1150:167-70. doi: 10.1196/annals.1447.038.

Apoptotic non-beta cells suppress beta cell antigen-reactive T cells and induce beta cell antigen-specific regulatory T cells.

Author information

  • 1Department of Pathology, Laboratory Medicine, University of Florida, Gainesville, Florida 32610, USA.


Steady-state cell apoptosis plays an important role in maintenance of self-tolerance. Based on this notion, the use of apoptotic cells to restore self-tolerance to beta cell antigens is a rational approach to type 1 diabetes (T1D) prevention. Our previous study demonstrated that transfusion of apoptotic beta cells induced immune tolerance to beta cell antigens in NOD mice. However, concerned about the limited beta cell source for future clinical applications, we attempted in the present study to develop a more practical approach for T1D prevention using apoptotic non-beta cells. We found that UVB-irradiation-induced apoptotic NOD splenic stromal cells significantly suppressed beta cell antigen-specific T cell proliferation in vitro and in vivo. Furthermore, TCR-transgenic CD4(+) T cells primed by the antigens to which they were specific in the presence of UVB-irradiated stromal cells were rendered unresponsive to the antigen restimulation, a result that was partially attributed to the induced IL-10-producing regulatory T cells. Of more interest, transfusion of UVB-irradiated stromal cells appeared to induce beta cell antigen-responding IL-10-producing regulatory T cells in vivo. Most importantly, transfusion of UVB-irradiated stromal cells effectively prevented T1D in NOD mice, which is consistent with these findings. This study suggests that it is possible to use apoptotic non-beta cells such as peripheral blood mononuclear cells to induce beta cell antigen-specific tolerance, thereby preventing T1D in humans.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Write to the Help Desk