The CD28/B7 interaction is not required for resistance to Toxoplasma gondii in the brain but contributes to the development of immunopathology.
Infection of C57BL/6 mice with Toxoplasma gondii leads to chronic encephalitis characterized by infiltration into the brain of T cells that produce IFN-gamma and mediate resistance to the parasite. Our studies revealed that expression of B7.1 and B7.2 was up-regulated in brains of mice with toxoplasmic encephalitis (TE). Because CD28/B7-mediated costimulation is important for T cell activation, we assessed the contribution of this interaction to the production of IFN-gamma by T cells from brains and spleens of mice with TE. Stimulation of splenocytes with Toxoplasma Ag or anti-CD3 mAb resulted in production of IFN-gamma, which was inhibited by 90% in the presence of CTLA4-Ig, an antagonist of B7 stimulation. However, production of IFN-gamma by T cells from the brains of these mice was only slightly reduced (20%) by the addition of CTLA4-Ig. To address the role of the CD28/B7 interaction during TE, we compared the development of disease in C57BL/6 wild-type (wt) and CD28-/- mice. Although the parasite burden was similar in wt and CD28-/- mice, CD28-/- mice developed less severe encephalitis and survived longer than wt mice. Ex vivo recall responses revealed that mononuclear cells isolated from the brains of chronically infected CD28-/- mice produced less IFN-gamma than wt cells, and this correlated with reduced numbers of intracerebral CD4+ T cells in CD28-/- mice compared with wt mice. Taken together, our data show that resistance to T. gondii in the brain is independent of CD28 and suggest a role for CD28 in development of immune-mediated pathology during TE.
Reichmann
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G
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
Villegas
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EN
Craig
L
L
Peach
R
R
Hunter
C A
CA
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018106:CD28 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002908:Chronic Disease; D004660:Encephalitis / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D005260:Female; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
D018122:B7-1 Antigen; D018106:CD28 Antigens