Frequencies of neuroantigen-specific T cells in the central nervous systemversus the immune periphery during the course of experimental allergic encephalomyelitis

Direct measurements of the frequency and the cytokine signature of the neur oantigen-specific effector cells in experimental allergic encephalomyelitis (EAE) are a continuing challenge. This is true for lymphoid tissues, and m ore importantly, for the CNS itself. Using enzyme-linked immunospot analysi s (ELISPOT) assays, we followed proteolipid protein (PLP) 139-151-specific T cells engaged by active immunization of SJL mice. The total numbers of PL P139-151-specific CD4 cells were highest before disease onset. At this time , these cells resided in lymphoid and nonlymphoid tissues, but were not det ected in the CNS. While the PLP139-151-specific cells reached high frequenc ies in the CNS during clinical EAE, in absolute numbers, less than 20% of t hem were present in the target organ, with the majority residing in the per iphery throughout all stages of the disease. The numbers of PLP139-151-spec ific cells gradually declined in both compartments with time. While eventua lly this first wave of effector cells completely disappeared from the CNS, PLP178-191-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 secon d wave of effector cells is engaged while the first wave undergoes exhausti on.