The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

TY - JOUR

T1 - The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

AU - Bregenholt, S

AU - Petersen, T R

AU - Claesson, Mogens Helweg

PY - 2001/8/1

Y1 - 2001/8/1

N2 - We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J. Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti-FasL antiserum for 12 h blocked the apoptotic process in lamina propria CD4(+) T-cells by more than 65% compared to mice treated with control antiserum. Together, these results point towards the Fas-FasL and not the TNF-alpha-TNF-alpha receptor system as the primary apoptosis-inducing mechanism of lamina propria CD4(+) T-cells in this model of murine chronic colitis, and suggest an important role for the Fas-FasL system in the maintenance of homeostasis of locally proliferating T-cells.

AB - We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J. Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti-FasL antiserum for 12 h blocked the apoptotic process in lamina propria CD4(+) T-cells by more than 65% compared to mice treated with control antiserum. Together, these results point towards the Fas-FasL and not the TNF-alpha-TNF-alpha receptor system as the primary apoptosis-inducing mechanism of lamina propria CD4(+) T-cells in this model of murine chronic colitis, and suggest an important role for the Fas-FasL system in the maintenance of homeostasis of locally proliferating T-cells.

KW - Adoptive Transfer

KW - Animals

KW - Antigens, CD95

KW - Apoptosis

KW - Basement Membrane

KW - CD4-Positive T-Lymphocytes

KW - Colitis, Ulcerative

KW - Cytotoxicity, Immunologic

KW - Disease Models, Animal

KW - Fas Ligand Protein

KW - Immune Sera

KW - Intestinal Mucosa

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, SCID

M3 - Journal article

C2 - 11470145

SN - 0165-2478

VL - 78

SP - 7

EP - 12

JO - Immunology Letters

JF - Immunology Letters

IS - 1

ER -