Abstract
The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of pregress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.
| Original language | English |
|---|---|
| Pages (from-to) | 316-322 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 97 |
| Issue number | 2 |
| Publication status | Published - Jan 15 1996 |
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Keywords
- Acidic sphingomyelinase
- CD95
- Fas/APO-1
- Gut mucosa
- T-LPL
ASJC Scopus subject areas
- Medicine(all)
Cite this
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. / De Maria, Ruggero; Boirivant, Monica; Cifone, Maria Grazia; Roncaioli, Paola; Hahne, Michael; Tschopp, Jurg; Pallone, Francesco; Santoni, Angela; Testi, Roberto.
In: Journal of Clinical Investigation, Vol. 97, No. 2, 15.01.1996, p. 316-322.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes
T2 - A potential role for the acidic sphingomyelinase pathway in normal immunoregulation
AU - De Maria, Ruggero
AU - Boirivant, Monica
AU - Cifone, Maria Grazia
AU - Roncaioli, Paola
AU - Hahne, Michael
AU - Tschopp, Jurg
AU - Pallone, Francesco
AU - Santoni, Angela
AU - Testi, Roberto
PY - 1996/1/15
Y1 - 1996/1/15
N2 - The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of pregress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.
AB - The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of pregress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.
KW - Acidic sphingomyelinase
KW - CD95
KW - Fas/APO-1
KW - Gut mucosa
KW - T-LPL
UR - http://www.scopus.com/inward/record.url?scp=0030050848&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030050848&partnerID=8YFLogxK
M3 - Article
C2 - 8567950
AN - SCOPUS:0030050848
VL - 97
SP - 316
EP - 322
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 2
ER -