Differential CD86/B7-2 expression and cytokine secretion induced by Toxoplasma gondii in macrophages from resistant or susceptible BALB H-2 congenic mice

The influence of the intracellular parasite Toxoplasma gondii on macrophage expression of costimulatory molecules was studied. Unlike surface expressi on of CD80/B7-1, that of CD86/B7-2 is increased in mouse peritoneal macroph ages 24 h following exposure to live toxoplasma in vitro. Most CD86 molecul es are found on infected cells bearing a maximum parasite load. Consistent with the elevated membrane expression, the quantity of CD86 gene transcript is increased in macrophages infected by T. gondii in vitro or in vivo. CD8 6 up-regulation contributes to the augmented capacity of parasitized macrop hages to present antigen to tuberculin-specific CD4(+) T cells as demonstra ted by blocking CD86 ligand interaction, T: gondii triggers up-regulation o f CD86 in macrophages from BALB/c mice which are resistant to the developme nt of toxoplasmic encephalitis. Infection of macrophages from the susceptib le strain BALB.B, however, results in a decreased surface expression of CD8 6, although the parasite load and intracellular proliferation proved compar able in both macrophages, This differential host cell reaction correlates w ith disparate profiles in T: gondii-induced cytokine secretion. Upon challe nge with toxoplasma, IL-la and tumor necrosis factor (TNF)-alpha are releas ed to a significantly higher extent by BALB/c than by BALB.B macrophages, w hereas the latter secrete more IL-12 and IL-10. In BALB.B macrophages, T: g ondii-induced IL-10 down-regulates surface expression of CD86, thus indicat ing an interference of parasite-dependent cytokine release and modulation o f CD86, The biased secretory response in macrophages from the two congenic strains implies an MHC-dependent and dichotomous monokine induction by T: g ondii, Up-regulation of CD86 seems to occur along the IL-1-TNF-inducing pat hway and experimental evidence indicates that this enhances T cell activati on by parasitized macrophages.