公开(公告)号：WO1996022370A1

公开(公告)日：1996-07-25

申请号：PCT/US1996000606

申请日：1996-01-19

Applicant: UAB RESEARCH FOUNDATION

Inventor： UAB RESEARCH FOUNDATION ,  MOUNTZ, John, D. ,  LIU, Changdan ,  CHENG, Jianhua ,  KOOPMAN, William, J. ,  ZHOU, Tong

IPC: C12N15/12

CPC classification number: A01K67/0275 ,  A01K2217/05 ,  A61K38/00 ,  C07K14/715 ,  C12N15/67 ,  C12N2799/022 ,  C12N2799/027

Abstract: Disclosed is a 5' flanking sequence of the human fas gene containing a promoter region. This sequence also contains at least three transcription initiation sites, as well as consensus sequences for AP-1, GF-1, NY-Y, CP-2, EB20, and c-myb. Also disclosed are methods of altering senescence of the immune system by modifying Fas activity in cells to increase or decrease apoptosis. Fas expression and function on T cells from old (22-26-month-old) mice is also compared to young (2-month-old) mice and old CD2-fas transgenic mice. Fas expression and ligand-induced apoptosis was decreased on T cells from old mice compared to young mice. In 26-month-old CD2-fas transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis and that the CD2-fas transgene allows the maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.

Abstract translation: 披露了含有启动子区的人fas基因的5'侧翼序列。 该序列还含有至少三个转录起始位点，以及AP-1，GF-1，NY-Y，CP-2，EB20和c-myb的共有序列。 还公开了通过改变细胞中的Fas活性来增加或减少凋亡来改变免疫系统衰老的方法。 将老年（22-26个月大）小鼠的T细胞的Fas表达和功能与年轻（2月龄）的小鼠和老的CD2-fas转基因小鼠进行比较。 与老年小鼠相比，来自老鼠的T细胞的Fas表达和配体诱导的凋亡降低。 在26个月大的CD2-fas转基因小鼠中，Fas和CD44表达，Fas诱导的凋亡，T细胞增殖和细胞因子产生与年轻小鼠相当。 这些结果表明，随着年龄的增长，T细胞衰老与细胞凋亡有关，CD2-fas转基因能够维持老年小鼠Fas细胞凋亡功能和T细胞功能，与年轻小鼠相当。

公开(公告)号：WO1996020206A1

公开(公告)日：1996-07-04

申请号：PCT/US1995017083

申请日：1995-12-22

Applicant: UAB RESEARCH FOUNDATION

Inventor： UAB RESEARCH FOUNDATION ,  MOUNTZ, John, D. ,  LIU, Changdan ,  ZHOU, Tong ,  CHENG, Jianhua

IPC: C07H21/04

CPC classification number: C07K14/715 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/32 ,  C12N15/62

Abstract: Disclosed is a natural, soluble form of the Fas antigen polypeptide that is secreted by human cells and is the result of alternative mRNA processing in the cell. This variant of Fas is shown to be present at higher levels in patients with SLE and AILD. Also disclosed are nucleic acids encoding this unique form of the Fas antigen and methods for making and using the protein and nucleic acids, including various diagnostic embodiments such as ELISAs.

Abstract translation: 公开了天然的可溶形式的Fas抗原多肽，其由人细胞分泌并且是细胞中替代的mRNA加工的结果。 Fas的这种变体在SLE和AILD患者中表现出更高的水平。 还公开了编码Fas抗原的这种独特形式的核酸和用于制备和使用蛋白质和核酸的方法，包括各种诊断实施例如ELISA。