The role of natural killer cells in the induction of autoimmune gastritis.
A number of experimental models of organ-specific autoimmunity involve a period of peripheral T cell lymphopenia prior to disease onset. In particular, experimental autoimmune gastritis, induced in susceptible mouse strains by neonatal thymectomy, is a CD4+ T cell mediated autoimmune disease. We have previously demonstrated that this disease displays the hallmarks of a Th1-mediated DTH inflammatory response with an essential role for IFN-gamma very early in the pathogenesis of disease. Given the interplay between the innate and adaptive immune responses, a potential source of early IFN-gamma production in these lymphopenic mice is the innate immune response. Here we have assessed the contribution of innate immunity to the induction of experimental autoimmune gastritis, in particular, the role of natural killer (NK) cells in production of IFN-gamma. Analysis of NK cells and macrophages revealed no difference in either the number or activation status between euthymic and neonatally thymectomised mice. Furthermore, in vivo depletion of NK cells immediately after neonatal thymectomy of (BALB/cCrSlcxC57BL/6) F1 mice demonstrated no reduction in disease incidence compared to control groups of neonatally thymectomised mice. Therefore, we conclude that NK cells are not the primary source of IFN-gamma required for the pathogenesis of autoimmune gastritis following neonatal thymectomy but rather the small cohort of T cells in the periphery of lymphopenic mice are likely to be responsible for the IFN-gamma production.
La Gruta
N L
NL
Department of Pathology and Immunology, Monash University Medical School, Melbourne, Vic, Australia.
Van Driel
I R
IR
Toh
B H
BH
Gleeson
P A
PA
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D005756:Gastritis / Q000209:etiology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013934:Thymectomy; D013950:Thymus Gland / Q000601:surgery