VCAM-1/α4β1 Integrin Interaction Is Crucial for Prompt Recruitment of Immune T Cells into the Brain during the Early Stage of Reactivation of Chronic Infection with Toxoplasma gondii To Prevent Toxoplasmic Encephalitis

Abstract

dReactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/␣4␤1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. 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 the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-␣4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3␦, CD4, CD8␤, gamma interferon (IFN-␥), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4 ؉ and CD8 ؉ T cells in the brain were significantly less in mice treated with anti-␣4 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-␣4 integrin antibody-treated than in control antibody-treated animals, even though IFN-␥ and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/␣4␤1 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-␥-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth.

Determination of a Key Antigen for Immunological Intervention To Target the Latent Stage of Toxoplasma gondii

“…Mononuclear cells were purified from brains of infected, sulfadiazine-treated SCID mice at 7 days after a systemic transfer of CD8 + immune T cells as described previously (16, 17). To determine TCR Vβ chain usage in the CD8 + immune T cells that had infiltrated into the brains of the recipient SCID mice, the purified mononuclear cells were first pretreated with anti-FcγII/III receptors mAb (clone 2.4G2) and then incubated with a PE-conjugated mAb to CD8α (clone 53–6.7) and FITC-conjugated mAb to various TCR Vβ chains as described previously (18).…”

MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1

“…As to the wide distribution of VCAM-1 in human tissues and organs, this molecule is implicated in a plenty of pathophysiological situations, which include autoimmune diseases [31], cardiovascular disease [32], or infections [33]. Recently, its function in tumor progression and metastasis has drawn increasing attentions.…”

CD8+ T cells remove cysts of Toxoplasma gondii from the brain mostly by recognizing epitopes commonly expressed by or cross-reactive between type II and type III strains of the parasite

“…RNA was purified from a half of each brain, and amounts of mRNA for BAG1, perforin, and granzyme B were measured by reverse transcription real-time PCR using StepOnePlus real-time PCR system with TaqMan reagents (Applied Biosystems, Branchburg, New Jersey) [7,13]. Primers and probe for BAG1 were as follows: TCACGTGGAGACCCAGAGT (Forward), CTGGCAAGT-CAGCCAAAATAATCAT (reverse), TTTGCTGTCGAAC TCC (probe) [17]. Primers and probes for perforin and granzyme B were from Applied Biosystems.…”