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CD1-Dependent Regulation of Chronic Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis ¹

Section for Medical Inflammation Research, Lund University, Lund, Sweden

The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1^-/- mice develop a clinically more severe and chronic EAE compared with CD1^+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1^-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1^+/+ and CD1^-/- mice but an amplified cytokine response in CD1^-/- mice as measured by both the Th1 cytokine IFN- and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-1-producing cells early in the disease in CD1^+/+ mice, which was absent in the CD1^-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1^-/- mice again developed an augmented EAE compared with CD1^+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance.

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