CYTOTOXIC T-CELLS DEFICIENT IN BOTH FUNCTIONAL FAS LIGAND AND PERFORIN SHOW RESIDUAL CYTOLYTIC ACTIVITY YET LOSE THEIR CAPACITY TO INDUCE LETHAL ACUTE GRAFT-VERSUS-HOST DISEASE
My. Braun et al., CYTOTOXIC T-CELLS DEFICIENT IN BOTH FUNCTIONAL FAS LIGAND AND PERFORIN SHOW RESIDUAL CYTOLYTIC ACTIVITY YET LOSE THEIR CAPACITY TO INDUCE LETHAL ACUTE GRAFT-VERSUS-HOST DISEASE, The Journal of experimental medicine, 183(2), 1996, pp. 657-661
Graft-versus-host disease (GVHD) is the main complication after alloge
neic bone marrow transplantation. Although the tissue damage and subse
quent patient mortality are clearly dependent on T lymphocytes present
in the grafted inoculum, the lethal effector molecules are unknown. H
ere, we show that acute lethal GVHD, induced by the transfer of spleno
cytes from C57BL/6 mice into sensitive BALB/c recipients, is dependent
on both perforin and Fas ligand (FasL)-mediated lytic pathways. When
spleen cells from mutant mice lacking both effector molecules were tra
nsferred to sublethally irradiated allogeneic recipients, mice survive
d. Delayed mortality was observed with grafted cells deficient in only
one lytic mediator. In contrast, protection from lethal acute GVHD in
resistant mice was exclusively perforin dependent. Perforin-FasL-defi
cient T cells failed to lyse most target cells in vitro. However, they
still efficiently killed tumor necrosis factor alpha-sensitive fibrob
lasts, demonstrating that cytotoxic T cells possess a third lytic path
way.