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.
Bennett
M
M
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Taylor
P A
PA
Austin
M
M
Baker
M B
MB
Schook
L B
LB
Rutherford
M
M
Kumar
V
V
Podack
E R
ER
Mohler
K M
KM
Levy
R B
RB
Blazar
B R
BR
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