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Frequencies of Neuroantigen-Specific T Cells in the Central Nervous System Versus the Immune Periphery During the Course of Experimental Allergic Encephalomyelitis¹

Oleg S. Targoni^2,*, Jan Baus^2,*,, Harald H. Hofstetter^*, Maike D. Hesse^*,, Alexey Y. Karulin^*, Bernhard O. Boehm, Thomas G. Forsthuber^* and Paul V. Lehmann^3,*

^* Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; and University Hospital of Ulm, Section of Endocrinology, Ulm, Germany

Direct measurements of the frequency and the cytokine signature of the neuroantigen-specific effector cells in experimental allergic encephalomyelitis (EAE) are a continuing challenge. This is true for lymphoid tissues, and more importantly, for the CNS itself. Using enzyme-linked immunospot analysis (ELISPOT) assays, we followed proteolipid protein (PLP) 139–151-specific T cells engaged by active immunization of SJL mice. The total numbers of PLP_139–151-specific CD4 cells were highest before disease onset. At this time, these cells resided in lymphoid and nonlymphoid tissues, but were not detected in the CNS. While the PLP_139–151-specific cells reached high frequencies in the CNS during clinical EAE, in absolute numbers, less than 20% of them were present in the target organ, with the majority residing in the periphery throughout all stages of the disease. The numbers of PLP_139–151-specific cells gradually declined in both compartments with time. While eventually this first wave of effector cells completely disappeared from the CNS, PLP_178–191-specific cells became engaged, being detected first in the CNS. These data suggest that throughout all stages of EAE, the effector cells in the CNS are recruited from a vast peripheral reservoir, and that the second wave of effector cells is engaged while the first wave undergoes exhaustion.

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