Influence of mouse colony environment on ability of perforin -/- (PKO) mice to reject TAP-1-/- marrow grafts

M. D. Austin, V. Kumar, M. Bennett, R. B. Levy, B. R. Blazar

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Murine NK cells may use cytokines and/or cytotoxic means for rejection of bone marrow cell (BMC) allografts. Focusing on perforin, 129:B6 (NK1.1 of B6 origin) PKO mice were irradiated and challenged with class 1 deficient TAP-1-/- BMC in which NK cells are the effectors. Growth of donor-derived cells was judged in terms of splenic incorporation of 125I-iodo-deoxyuridine 5 days after cell transfer. 129:B6 PKO mice maintained in a specific pathogen-free (spf) environment rejected TAP-1-/- BMC, which was prevented by anti-NK1.1 mAbs. However, the same mice housed in a conventional breeding facility failed to reject TAP-1-/- BMC. Transfer of mice from a spf to a conventional facility (or treatment of conventional mice with antibiotics), resulted in a slow, incomplete loss (or gain), respectively, in the ability to reject TAP-1-/- BMC. Thus, the breeding colony environment can elicit otherwise undetectable defects in the rejection ability of PKO NK cells. In contrast, the ability of B6 PKO mice to reject TAP-1-/- BMC is retained in a conventional colony. B6 PKO mice in spf conditions can reject allogeneic H2d BMC grafts, but this ability is lost in a conventional colony. This genetic differences between B6 and 129:B6 PKO mice, both identical for the B6-strain NK-1.1 genetic region, suggests that a different important immune-response-like gene regulates the ability of mice to reject BMC grafts by a perforin-independent mechanism.

Original languageEnglish (US)
Pages (from-to)A903
JournalFASEB Journal
Issue number5
StatePublished - Mar 20 1998


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