• animals show a significant reduction in overall diabetes incidence (14.6% vs ~50% in Tnfsf4-heterozygotes and wild-type) and increase in the age of onset (9.5 weeks vs 6 weeks in controls)

• mice are considered diabetic after a blood glucose measure of >300 mg/dl and 2 positive urine glucose tests

• mice survive beyond 3 to 4 weeks of age unlike Ctla4^tm1All homozygotes (J:109887)

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

• at 6 weeks, mice exhibit infiltration in the pancreas and spleen unlike in wild-type mice

• however, infiltration is not as severe or extensive as in Ctla4^tm1All homozygotes

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

• in the pancreas

• from CD4+ pancreatic T cells

• from CD4+ pancreatic T cells

• diabetes disease progression is abrogated compared to in control mice

• however, mice develop insulitis

• in the pancreas

• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice

• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice

• Il4-deficient transgenic NOD mice do not show early or frequent diabetes compared to control transgenic NOD mice

• the frequency of double positive T cell apoptosis in thymic lobes is increased compared to in similarly treated heterozygous mice

• fetal thymic organ cultures treated with BDC2.5 produce fewer double positive thymocytes than similarly treated heterozygous cells

• fetal thymic organ cultures treated with BDC2.5 produce more CD8+ single positive thymocytes than similarly treated heterozygous cells

• fetal thymic organ cultures treated with BDC2.5 produce fewer double positive thymocytes than similarly treated heterozygous cells

• fetal thymic organ cultures treated with BDC2.5 produce more CD8+ single positive thymocytes than similarly treated heterozygous cells

• the frequency of double positive T cell apoptosis in thymic lobes is increased compared to in similarly treated heterozygous mice

• fetal thymic organ cultures treated with BDC2.5 produce fewer double positive thymocytes than similarly treated heterozygous cells

• peri-islet Schwann cells are intact and surround remaining alpha-cells in contrast to control wild-type NOD mice (J:135214)

• treatment with anti-PDCA-1, which depleted plasmocyoid dendritic cells, or 1MT, which neutralize indoleamine 2,3 dioxygenase production, increases the severity of insulitis

• treatment with anti-PDCA-1 ablates the plasmocytoid dendritic cell population within the pancreatic lymph nodes

• treatment with anti-PDCA-1, which depleted plasmocyoid dendritic cells, or 1MT, which neutralize indoleamine 2,3 dioxygenase production, increases the severity of insulitis

• treatment with anti-PDCA-1 ablates the plasmocytoid dendritic cell population within the pancreatic lymph nodes

• insulitis begins abruptly between days 15 and 18 after birth; at 14 days after birth, few activated (CD69+) T cells are detected

• in transgenic mice, a large proportion of cells in the pancreatic lymph nodes and pancreatic islets have an activated phenotype (CD4+ Vbeta4+) compared to nontransgenic littermates

• adoptive tranfer of splenocytes from transgenic mice carrying the Tg(TcraBDC2.5)1Doi transgene into knockout recipients led to diabetes after a significant delay compared to diabetes development in wild-type recipients (100% in wild-type by 12 days versus 100% in knockouts by 20 days)

• insulitis begins abruptly between days 15 and 18 after birth; at 14 days after birth, few activated (CD69+) T cells are detected

• in transgenic mice, a large proportion of cells in the pancreatic lymph nodes and pancreatic islets have an activated phenotype (CD4+ Vbeta4+) compared to nontransgenic littermates