apoptosis of purified cd4+ t cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic nod mice纯化cd4 + t细胞的凋亡是由细胞因子子集不足和缺乏其他细胞的新发糖尿病nod老鼠.pdf

Apoptosis of Purified CD4+ T Cell Subsets Is Dominated by Cytokine Deprivation and Absence of Other Cells in New Onset Diabetic NOD Mice 1,4 5 1,3 1,2 1 Ayelet Kaminitz , Enosh M. Askenasy , Isaac Yaniv , Jerry Stein , Nadir Askenasy * 1 Frankel Laboratory, Center for Stem Cell Research, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, 2 Bone Marrow Transplant Unit, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, 3 Department of Pediatric Hematology-Oncology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, 4 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 5 Soroka Medical School, Ben-Gurion University of the Negev, Beer Sheva, Israel Abstract Background: Regulatory T cells (Treg) play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. Principal Findings: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25+ T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD252 T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2