Requirement of non-T cells that produce gamma interferon for prevention of reactivation of Toxoplasma gondii infection in the brain.
We examined the mechanism of resistance against reactivation of infection with Toxoplasma gondii in the brain. BALB/c-background gamma interferon (IFN-gamma)-knockout (IFN-gamma(-/-)) and control mice were infected and treated with sulfadiazine beginning 4 days after infection for 3 weeks. After discontinuation of treatment, IFN-gamma(-/-) mice succumbed to toxoplasmic encephalitis (TE) and died, whereas control animals did not develop TE and survived. Adoptive transfer of immune spleen cells from infected control mice did not prevent development of TE or mortality in the IFN-gamma(-/-) mice. To examine whether the failure of the cell transfer to protect against TE is unique to IFN-gamma(-/-) mice, athymic nude and SCID mice that lack T cells were infected and injected with the immune spleen or T cells in the same manner as IFN-gamma(-/-) mice. Whereas control nude and SCID mice that had not received the immune cells developed severe TE and died after discontinuation of sulfadiazine, those that had received the cells did not develop TE and survived. Before cell transfer, IFN-gamma mRNA was detected in brains of infected nude and SCID but not in brains of IFN-gamma(-/-) mice. IFN-gamma mRNA was also detected in brains of infected SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibody, and such animals did not develop TE after receiving immune T cells. Thus, IFN-gamma production by non-T cells, in addition to T cells, is required for prevention of reactivation of T. gondii infection in the brain. The IFN-gamma-producing non-T cells do not appear to be NK cells.
Kang
H
H
Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 94301, USA.
Suzuki
Y
Y
D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D012333:RNA, Messenger / Q000032:analysis; D016781:Toxoplasmosis, Cerebral / Q000517:prevention & control*
D012333:RNA, Messenger; D007371:Interferon-gamma