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Experimental autoimmune meningitis: a novel neurological disease in CD28-deficient mice
P J Perrin1, E Lavi, C A Rumbley
1Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
C57BL/6 mice develop T-cell-mediated experimental autoimmune encephalomyelitis (EAE) after immunization with the neuroantigen myelin oligodendrocyte glycoprotein. (MOG). We immunized CD28-deficient C57BL/6 mice to determine the role of T cell costimulation in the immune response to MOG. CD28-/- mice developed experimental autoimmune meningitis (EAM). EAM is a fatal, acute disease characterized by simultaneous weakness in all limbs, photophobia, irritability, and spatial disorientation. Histologically, EAM consisted of an infiltrate of myeloid, monocytic, and lymphocytic leukocytes within the leptomeninges. In contrast, the brain parenchyma was unaffected. EAM was mediated by CD4+ T cells since CD4 depletion prevented the disease. Upon rechallenge, mice in which EAM was prevented by CD4+ cell depletion developed EAE not EAM. Therefore, the presence or absence of CD28 determines the initial phenotype of the immune response to MOG. EAM, which develops in the absence of CD28, is a unique experimental model for immune-mediated aseptic meningitis.
Insights
Mice lacking CD28 develop fatal experimental autoimmune meningitis (EAM) instead of experimental autoimmune encephalomyelitis (EAE) when exposed to MOG. CD28 absence dictates the autoimmune disease phenotype, highlighting its role in T-cell costimulation.
Area of Science:
- Neuroimmunology
- Autoimmunity
- T-cell immunology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated disease induced by neuroantigens like myelin oligodendrocyte glycoprotein (MOG).
- T-cell costimulation is crucial for adaptive immune responses, but its specific role in MOG-induced autoimmunity is not fully understood.
Purpose of the Study:
- To investigate the role of T-cell costimulation, specifically via CD28, in the development of autoimmune responses to MOG.
- To characterize the disease phenotype in CD28-deficient mice immunized with MOG.
Main Methods:
- Immunization of C57BL/6 mice, including CD28-deficient (CD28-/-) mice, with myelin oligodendrocyte glycoprotein (MOG).
- Clinical and histological assessment of disease development.
- T-cell depletion studies (CD4+ T cells) to determine disease mediation.
- Rechallenge experiments to assess disease phenotype plasticity.
Main Results:
- CD28-/- mice developed a fatal acute disease, experimental autoimmune meningitis (EAM), characterized by leptomeningeal inflammation and neurological symptoms.
- EAM was mediated by CD4+ T cells.
- Prevention of EAM via CD4+ T-cell depletion followed by rechallenge resulted in the development of EAE, not EAM.
- The absence of CD28 determined the initial disease phenotype.
Conclusions:
- CD28 signaling is critical in determining the phenotype of T-cell-mediated autoimmune responses to MOG.
- Experimental autoimmune meningitis (EAM) in CD28-deficient mice represents a distinct model of immune-mediated meningitis.
- This study highlights the pivotal role of CD28 in directing autoimmune responses towards either encephalomyelitis or meningitis.