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 DC), that might be related to islet autoimmunity. The immunophenotype of NOD splenic DC did not show significant abnormalities as compared with the immunophenotype 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 C57BL/10 and BALB/c mice. The allogeneic response induced by NOD DC was similar to or only slightly lower than the response induced by C57BL/10 DC. Both a normal immunophenotype of NOD DC and efficient T cell stimulation were observed regardless of the stage of diabetes development. However, 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 demonstrated that during the interaction of NOD cells fewer apoptotic cells were generated as compared with the interaction of C57BL/10 cells. Thus, the prolonged T cell response during the syngeneic interaction between NOD DC and T cells might be due to an impaired apoptosis induction. The impaired apoptosis might be of critical importance in the development of islet autoimmunity in the NOD mouse.
Radosevic
K
K
Department of Immunology, Erasmus University Rotterdam, The Netherlands. radosevic@immu.fgg.eur.nl
Casteels
K M
KM
Mathieu
C
C
Van Ewijk
W
W
Drexhage
H A
HA
Leenen
P J
PJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1