Experimental Autoimmune Meningitis: A Novel Neurological Disease in CD28-Deficient Mice

Pj, Perrin; Lavi, Ehud; Ca, Rumbley; Sa, Zekavat; Phillips, Stuart M.

doi:10.1006/clim.1998.4684

Cited by 24 publications

(13 citation statements)

References 57 publications

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“…Our findings with OX40-OX40L blockade, however, support a unique role for this pathway in CD28-independent costimulation in EAE. An interesting aspect of EAE induction in CD28KO mice is the accumulation of cells in the meninges and within blood vessels, as we show here and as was previously described (58). In addition, delayed-type hypersensitivity responses to the immunizing antigen were impaired in these mice (26), suggesting a problem with trafficking of antigen-specific cells.…”

Section: Discussionsupporting

confidence: 79%

CD28-independent induction of experimental autoimmune encephalomyelitis

Chitnis

Najafian²,

Abdallah³

et al. 2001

J. Clin. Invest.

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Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated disease initiated by antigenspecific CD4 + T cells. Signaling through CD28 is a critical second signal for activation of T cells, and CD28 knockout (CD28KO) mice have been reported to be resistant to induction of EAE. We now report that CD28KO mice have no intrinsic defect in mediating disease, because they developed EAE after passive transfer of primed T cells. After immunization, peripheral T cells from CD28KO mice were primed and developed memory phenotype, but had decreased antigen-specific IFN-γ production as compared with cells from wild-type (WT) animals. Reimmunization of CD28KO mice brought out clinical disease and increased IFN-γ production in vitro. Pathologically, there were cellular infiltrates in the central nervous system, in contrast to single-immunized mice. We show furthermore that blocking B7-1 or CTLA4, but not B7-2, in CD28KO mice induces disease after a single immunization. Thus, EAE can be induced in animals lacking CD28-dependent costimulation, suggesting that alternative costimulatory pathways were used. Blocking the OX40-OX40L costimulatory pathway differentially affected disease induction in CD28KO mice as compared with WT controls. Our data show that EAE may develop in the absence of CD28 T-cell costimulation. These findings have implications for therapies aimed at blocking costimulatory signals in autoimmune diseases.

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Section: Discussionsupporting

confidence: 79%

CD28-independent induction of experimental autoimmune encephalomyelitis

Chitnis

Najafian²,

Abdallah³

et al. 2001

J. Clin. Invest.

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“…CD28-deficient mice are resistant to actively induced experimental autoimmune encephalomyelitis (EAE) (1)(2)(3)(4). Interestingly, T cells from CD28 -/-mice can be primed to antigen and can develop an effector/memory phenotype (4).…”

Section: Introductionmentioning

confidence: 99%

Regulatory functions of CD8+CD28– T cells in an autoimmune disease model

Najafian¹,

Chitnis²,

Salama³

et al. 2003

J. Clin. Invest.

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“…We previously reported that CD28-deficient C57BL/6 mice (CD28 Ϫ/Ϫ ) develop experimental autoimmune meningitis (EAM) following primary immunization with myelin/oligodendrocyte glycoprotein (MOG) (7). EAM is a fatal, acute disease characterized by generalized simultaneous weakness in all limbs, spatial disorientation, irritability, and photophobia.…”

Section: Introductionmentioning

confidence: 99%

“…Both EAM and EAE are dependent upon CD4 ϩ T cells (7,12). The cellularity and anatomical locations of the lesions, however, are different and reflect the resultant clinical disease phenotypes.…”

Section: Introductionmentioning

confidence: 99%