TCR Vβ8+ T Cells Prevent Development of Toxoplasmic Encephalitis in BALB/c Mice Genetically Resistant to the Disease

Abstract

BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vβ chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vβ8+ cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vβ6+ T cells were more prevalent than Vβ8+ T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vβ8+ immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vβ6+ immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vβ8+ immune T cells was greater than that of the total Vβ8− population. In addition, Vβ8+ immune T cells produced markedly greater amounts of IFN-γ than did the Vβ8− population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vβ8+ T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

“…Indeed, it was demonstrated that a higher frequency of Vβ8 chain in T lymphocytes was associated with BALB/c (H2 d ) resistance against TE caused by ME49, whereas preferential Vβ6 chain usage corelated with susceptibility in CBA/Ca (H2 k ). Adoptive transfer of BALB/c Vβ8 + , but not Vβ6 + , T cells was capable to prevent mortality and encephalitis in nude mice (Kang et al 2003, Wang et al 2005. Another evidence of the importance of cell-mediated effector mechanisms is that neutralization of IFN-γ or TNF-α and inhibition of NOS2 leads to reactivation of chronic infection with ME49 and results in encephalitis and uveitis (Gazzinelli et al 1992, 1993a, 1994a, Hayashi et al 1996a.…”

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

“…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). The mAbs were from BD Bioscience, and the staining was performed using pooled cells from the mice due to availability of only limited numbers of cells from the brain of each animal.…”

Granzyme B Expression by CD8+ T Cells Is Required for the Development of Experimental Cerebral Malaria

“…The brain is uniquely isolated from its own vasculature by the blood-brain barrier (BBB) (26), and yet CD8 + T cells in the bloodstream can cross into brain parenchymal tissue during infection (27,28), cancer (29)(30)(31), and autoimmune disease (32,33). Recent studies report that local antigenic stimulation may be required either for CD8 + T cell retention and motility arrest in brain microvasculature or crossing the BBB (34)(35)(36).…”