Splenic dendritic cells from the non-obese diabetic mouse induce a prolonged proliferation of syngeneic T cells. A role for an impaired apoptosis of NOD T cells?

In this study we have tried to detect abnormalities in the immunophenotype and/or function of dendritic cells from the non-obese diabetic mouse (NOD D C), that might be related to islet autoimmunity. The immunophenotype of NOD splenic DC did not show significant abnormalities as compared with the imm unophenotype of splenic DC from C57BL/10 mice. Furthermore, NOD splenic and lymph node DC stimulated proliferation of syngeneic T cells as efficiently as DC from C578L/10 and BALB/c mice. The allogeneic response induced by NO D DC was similar to or only slightly lower than the response induced by C57 BL/10 DC. Both a normal immunophenotype of NOD DC and efficient T cell stim ulation were observed regardless of the stage of diabetes development. Howe ver, the syngeneic T cell proliferation induced by NOD splenic DC, but not by C57BL/10 splenic DC, was significantly prolonged, and it was accompanied by an increased proportion of activated/memory CD4(+) cells. We demonstrat ed that during the interaction of NOD cells fewer apoptotic cells were gene rated as compared with the interaction of C57BL/10 cells. Thus, the prolong ed T cell response during the syngeneic interaction between NOD DC and T ce lls might be due to an impaired apoptosis induction. The impaired apoptosis might be of critical importance in the development of islet autoimmunity i n the NOD mouse. (C) 1999 Academic Press.