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Transfusion of Apoptotic ß Cells Induces Immune Tolerance to ß Cell Antigens and Prevents Type 1 Diabetes in NOD Mice

¹Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610, USA

Correspondence: xia{at}pathology.ufl.edu

Correspondence: salzler{at}pathology.ufl.edu

OBJECTIVE:In vivo induction of ß cell apoptosis has been demonstrated to be effective in preventing type 1 diabetes (T1D) in NOD mice. Based upon the notion that steady-state cell apoptosis is associated with self-tolerance, and the need for developing a more practical approach using apoptotic ß cells to prevent T1D, the current study is designed to investigate apoptotic ß cells induced ex vivo in preventing T1D.

RESEARCH DESIGN AND METHODS:NIT-1 cell line serves as a source of ß cells. Apoptotic NIT-1 cells are prepared by ultraviolet B (UVB) irradiation. Three weekly transfusions of UVB-NIT-1 (1x 10⁵/mouse) or PBS are employed to determine whether transfusions of UVB-NIT-1 induce immune tolerance to ß cell antigens in vivo, and prevent T1D. The suppression of anti-ß cell antibodies, polarization of Th cells and induction of regulatory T cells by UVB-NIT-1 treatment are investigated.

RESULTS:The transfusions of apoptotic NIT-1 cells suppress anti-ß cell antibody development, and induce Th2 responses and IL-10-producing Tr1 cells. Importantly, this treatment significantly delays and prevents the onset of diabetes when 10-week old NOD mice are treated. Adoptive transfer of splenocytes from UVB-NIT-1-treated mice prevents diabetes caused by simultaneously injected diabetogenic splenocytes in NOD-Rag-/- mice. Moreover, the proliferation of adoptively transferred CFSE-labeled ß-cell antigen-specific TCR-transgenic T cells in UVB-NIT-1-treated mice is markedly suppressed.

CONCLUSIONS:The transfusion of apoptotic ß cells effectively protects T1D in NOD mice by inducing immune tolerance to ß cell antigens. This approach has a great potential for immune intervention of human T1D.

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