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

We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Coliti s is accompanied by activation and apoptosis of Fas ligand and TNF-alpha ex pressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J. Imm unol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that fresh ly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mas tocytoma cells in a TCR/CD3 redirected chromium-release assay, but do not e xpress TNF-a mediated cytotoxicity. Pre-incubation of the isolated lamina p ropria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL sy stem 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 antise rum. Together, these results point towards the Fas-FasL and not the TNF-alp ha -TNF-alpha receptor system as the primary apoptosis-inducing mechanism o f lamina propria CD4(+) T-cells in this model of murine chronic colitis, an d suggest an important role for the Fas-FasL system in the maintenance of h omeostasis of locally proliferating T-cells. (C) 2001 Elsevier Science B.V. All rights reserved.