Cytokine and cytotoxic pathways of NK cell rejection of class I-deficient bone marrow grafts: influence of mouse colony environment.
Mouse NK cells may use both cytokine, e.g. IFN-gamma, tumor necrosis factor (TNF)-alpha and IL-12, and cytotoxic, e.g. perforin and Fas-FasL, pathways to reject incompatible bone marrow cell (BMC) grafts. To begin a dissection of these two major pathways, mice bearing deletional mutations of IFN-gamma, TNF-RI/II or perforin, or mice treated with mAb to IL-12, IFN-gamma or NK1.1 were irradiated and challenged with class I-deficient BMC grafts, a system in which only NK cells are the effector cells. Proliferation of the donor-derived cells was judged in terms of splenic incorporation of [125I]iododeoxyuridine 5 or 7 days after cell transfer. All of these mice maintained in a specific pathogen-free (s.p.f.) environment were able to reject the BMC, except those treated with anti-NK1.1 mAb. However, perforin deficient mice maintained in a conventional breeding facility failed to reject class I (Tap-1)-deficient marrow cells. Transfer of mice from the pathogen-free to the conventional facility resulted in a slow and incomplete loss of the ability to reject marrow cells. Thus, the breeding colony environment can elicit otherwise undetectable defects in the rejection ability of perforin-deficient NK cells. This report will hopefully alert those investigators who have only studied immune gene knockout mice in s.p.f. facilities and found no significant abnormalities.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
M
M
Bennett
P A
PA
Taylor
M
M
Austin
M B
MB
Baker
L B
LB
Schook
M
M
Rutherford
V
V
Kumar
E R
ER
Podack
K M
KM
Mohler
R B
RB
Levy
B R
BR
Blazar
D000818:Animals; D000911:Antibodies, Monoclonal; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003603:Cytotoxins / Q000276:immunology / Q000378:metabolism*; D004781:Environmental Exposure; D006084:Graft Rejection / Q000276:immunology*; D006799:Housing, Animal; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D016207:Cytokines; D003603:Cytotoxins