Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis

被引:113
作者
Boirivant, M
Pica, R
DeMaria, R
Testi, R
Pallone, F
Strober, W
机构
[1] UNIV ROMA LA SAPIENZA,GI UNIV,ROME,ITALY
[2] UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY
[3] UNIV REGGIO CALABRIA,DEPT EXPT MED,CATANZARO,ITALY
[4] NIAID,NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD
关键词
apoptosis; T lymphocytes; human intestinal lamina propria; regional immunity;
D O I
10.1172/JCI119082
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Lamina propria (LP)T cells respond poorly to a proliferative stimulus delivered via TCR/CD3 pathway, but retain considerable ability to respond to a stimulus delivered via CD2 costimulatory or accessory pathway. in the present study, we showed first that unstimulated LP T cells, as compared to unstimulated peripheral blood (PB)T cells, exhibit an increased level of apoptosis which is further increased following CD2 pathway stimulation, but not following via TCR/CD3 pathway stimulation. We next showed that IL-2 had a sparing effect on apoptosis of unstimulated LP T cells in that IL-2 decreased and anti-IL-2 increased apoptosis of these cells; in contrast, IL-2 had no effect on apoptosis of CD2-pathway stimulated eels. Finally, we showed that increased apoptosis of LP T cells induced by CD2-pathway stimulation is inhibited when Fas antigen is blocked by a nonstimulatory anti-Fas antibody. These studies suggest that LP T cells are characterized by increased susceptibility to Fas-mediated apoptosis most due to a downstream change in the Fas signaling pathway. Given that IFN-gamma secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may represent a mechanism of regulating detrimental immune responses in the mucosal environment.
引用
收藏
页码:2616 / 2622
页数:7
相关论文
共 35 条
[1]   FAS LIGAND MEDIATES ACTIVATION-INDUCED CELL-DEATH IN HUMAN T-LYMPHOCYTES [J].
ALDERSON, MR ;
TOUGH, TW ;
DAVISSMITH, T ;
BRADDY, S ;
FALK, B ;
SCHOOLEY, KA ;
GOODWIN, RG ;
SMITH, CA ;
RAMSDELL, F ;
LYNCH, DH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (01) :71-77
[2]   FAS TRANSDUCES ACTIVATION SIGNALS IN NORMAL HUMAN T-LYMPHOCYTES [J].
ALDERSON, MR ;
ARMITAGE, RJ ;
MARASKOVSKY, E ;
TOUGH, TW ;
ROUX, E ;
SCHOOLEY, K ;
RAMSDELL, F ;
LYNCH, DH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) :2231-2235
[3]   REVERSAL OF INVITRO T-CELL CLONAL ANERGY BY IL-2 STIMULATION [J].
BEVERLY, B ;
KANG, SM ;
LENARDO, MJ ;
SCHWARTZ, RH .
INTERNATIONAL IMMUNOLOGY, 1992, 4 (06) :661-671
[4]  
Boirivant M, 1996, P ASSOC AM PHYSICIAN, V108, P55
[5]   CD2 IS INVOLVED IN MAINTENANCE AND REVERSAL OF HUMAN ALLOANTIGEN-SPECIFIC CLONAL ANERGY [J].
BOUSSIOTIS, VA ;
FREEMAN, GJ ;
GRIFFIN, JD ;
GRAY, GS ;
GRIBBEN, JG ;
NADLER, LM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (05) :1665-1673
[6]   IMMUNOBIOLOGY AND IMMUNOPATHOLOGY OF HUMAN GUT MUCOSA - HUMORAL IMMUNITY AND INTRAEPITHELIAL LYMPHOCYTES [J].
BRANDTZAEG, P ;
HALSTENSEN, TS ;
KETT, K ;
KRAJCI, P ;
KVALE, D ;
ROGNUM, TO ;
SCOTT, H ;
SOLLID, LM .
GASTROENTEROLOGY, 1989, 97 (06) :1562-1584
[7]   CELL-AUTONOMOUS FAS (CD95) FAS-LIGAND INTERACTION MEDIATES ACTIVATION-INDUCED APOPTOSIS IN T-CELL HYBRIDOMAS [J].
BRUNNER, T ;
MOGIL, RJ ;
LAFACE, D ;
YOO, NJ ;
MAHBOUBI, A ;
ECHEVERRI, F ;
MARTIN, SJ ;
FORCE, WR ;
LYNCH, DH ;
WARE, CF ;
GREEN, DR .
NATURE, 1995, 373 (6513) :441-444
[8]   ISOLATION AND FUNCTIONAL CHARACTERIZATION OF HUMAN INTESTINAL MUCOSAL LYMPHOID-CELLS [J].
BULL, DM ;
BOOKMAN, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1977, 59 (05) :966-974
[9]   APOPTOTIC SIGNALING THROUGH CD95 (FAS/APO-1) ACTIVATES AN ACIDIC SPHINGOMYELINASE [J].
CIFONE, MG ;
DEMARIA, R ;
RONCAIOLI, P ;
RIPPO, MR ;
AZUMA, M ;
LANIER, LL ;
SANTONI, A ;
TESTI, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (04) :1547-1552
[10]   Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes - A potential role for the acidic sphingomyelinase pathway in normal immunoregulation [J].
DeMaria, R ;
Boirivant, M ;
Cifone, MG ;
Roncaioli, P ;
Hahne, M ;
Tschopp, J ;
Pallone, F ;
Santoni, A ;
Testi, R .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (02) :316-322