Allograft Rejection from Perforin and Fas Ligand Double-Deficient Mice

Abstract

In 2002, we demonstrated in this meeting that allograft-induced cytotoxic T lymphocytes (CTLs) were highly cytotoxic against allografted lymphoid cells, P815 mastocytoma cells, and fibroblasts but were inactive toward skin, KLN205 squamous carcinoma cells, and Meth A fibrosarcoma cells. In the present study, we examined the role of perforin and Fas ligand (FasL), both of which are known as the major effector molecules of CTL, in the rejection of CTL-susceptible P815 (H-2^d) cells from gld (a mutation of FasL), perforin knockout (KO), perforin/FasL double-deficient (dd) or control C57BL/6 (H-2^b) mice. When P815 cells were i.p. transplanted into gld, perforin KO, dd or control mice, they acutely rejected the allograft with similar time courses after transplantation; and host cells infiltrating into the rejection site exhibited similar cytotoxic activities against the allografted cells in a 12-h assay, whereas the cytotoxic activities of perforin KO or dd mice were less than10% of those from control mice in a 4-h assay, suggesting an important role of perforin in the early phase of cytotoxic activity. In addition, the cytotoxic activities of dd mice suggested the involvement of adhesive molecules in the cytotoxic mechanism. These results taken together indicate that most of in vivo CTL activity against allografted P815 cells appeared to be dependent on a third mechanism, one other than perforin- and FasL-based pathways. [Jpn J Physiol 54 Suppl:S85 (2004)]