Regulation of Experimental Autoimmune Encephalomyelitis in the C57BL/6J Mouse by NK1.1+, DX5+, αβ+ T Cells

Abstract

C57BL/6 (B6) mice with targeted mutations of immune function genes were used to investigate the mechanism of recovery from experimental autoimmune encephalomyelitis (EAE). The acute phase of passive EAE in the B6 mouse is normally resolved by partial recovery followed by mild sporadic relapses. B6 TCR β-chain knockout (KO) recipients of a myelin oligodendrocyte glycoprotein p35–55 encephalitogenic T cell line failed to recover from the acute phase of passive EAE. In comparison with wild-type mice, active disease was more severe in β2-microglobulin KO mice. Reconstitution of TCR β-chain KO mice with wild-type spleen cells halted progression of disease and favored recovery. Spleen cells from T cell-deficient mice, IL-7R KO mice, or IFN-γ KO mice were ineffective in this regard. Irradiation or treatment of wild-type spleen cell population with anti-NK1.1 mAb before transfer abrogated the protective effect. Removal of DX5+ cells from wild-type spleen cells by anti-DX5 Ab-coated magnetic beads before reconstitution abrogated the suppressive properties of the spleen cells. TCR-deficient recipients of the enriched DX5+ cell population recovered normally from passively induced acute disease. DX5+ cells were sorted by FACS into DX5+ αβTCR+ and DX5+ αβTCR− populations. Only recipients of the former recovered normally from clinical disease. These results indicate that recovery from acute EAE is an active process that requires NK1.1+, DX5+ αβ+ TCR spleen cells and IFN-γ.

Interleukin-6, Produced by Resident Cells of the Central Nervous System and Infiltrating Cells, Contributes to the Development of Seizures following Viral Infection

“…As a means of determining the contributions made by NK cells to the development of seizures in our TMEV-induced seizure model, infected mice were treated in vivo with the anti-NK1.1 antibody, which recognizes the NK1.1 surface antigen expressed on NK cells in the C57BL/6 strain of mice (15,44). This treatment has been shown to deplete splenic NK cells (to Ͻ0.08% of untreated levels) for up to 4 days following infection with murine cytomegalovirus (44).…”

Interdependency of MHC Class II/Self-Peptide and CD1d/Self-Glycolipid Presentation by TNF-Matured Dendritic Cells for Protection from Autoimmunity

“…All studies using ␣-GalCer as adjuvant to enhance immunity by inducing DC maturation in vivo (28,56,57) or for treatment of EAE (21)(22)(23) left questions open regarding which type or types of APCs are mediating these polarizing effects on NKT cells. Our data suggest that semimature TNF-DCs can bridge T cells with innate CD1d-dependent NKT cells by the induction of type 2 cytokine secretion by T and NKT cells, which leads in our model to the induction of protective IL-10 ϩ CD4 ϩ T cells.…”

CD1d-Dependent NKT Cells Play a Protective Role in Acute and Chronic Arthritis Models by Ameliorating Antigen-Specific Th1 Responses

“…CD1d-restricted NKTs have been described as fast, potent cytokine producers; when stimulated in vitro, they rapidly release large quantities of cytokines, including IL-4 and IFN-g (17)(18)(19)(20). These cells have been implicated as regulators in inflammatory autoimmunity due to their potential to rapidly secrete cytokines, both in human diseases such as diabetes (21) and multiple sclerosis (22)(23)(24), as well as in their animal model counterparts (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). But their role in suppressing *Neuroinflammation Unit, Department of Clinical Sciences, University of Lund, Lund, Sweden; and autoimmune diseases remains disputed, as several conflicting reports point toward a dichotomous influence of NKTs as being both beneficial or detrimental for the host (40,41).…”