VCAM-1/α4β1 integrin interaction is important for T cell recruitment to prevent reactivation of chronic infection with Toxoplasma gondii in the brain (P3326)

Abstract

Abstract T. gondii establishes a chronic infection by forming cysts preferentially in the brain, and IFN-γ production by T cells is required to maintain the latency of infection. We examined the adhesion molecules important for T cell recruitment to prevent reactivation of the infection. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of these animals as well as those of infected wild-type animals. We did not detect endothelial E-selectin, P-selectin, MAdCAM-1 or PNAd in any of the brains. Immune T cells from wild-type mice were treated with anti-α4 integrin or control mAbs and transferred into infected SCID or nude mice, and animals received the same mAb every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Cerebral expression of mRNA for CD3, CD4, CD8, IFN-γ, and NOS2 (an effector molecule to inhibit T. gondii growth) was 5-34 times less in mice treated with anti-α4 integrin mAb than those treated with control mAb at 3 days after sulfadiazine discontinuation. Amounts of tachyzoite (acute stage form of T. gondii)-specific SAG1 mRNA were 17 times greater in the former than the latter at 6 days after sulfadiazine discontinuation. These results indicate that VCAM-1/α4β1 integrin interaction is crucial for recruiting immune T cells into the brain to prevent reactivation of chronic T. gondii infection.