ANTIGEN-SPECIFIC DOWN-REGULATION OF MYELIN BASIC PROTEIN-REACTIVE T-CELLS DURING SPONTANEOUS-RECOVERY FROM EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - FURTHER EVIDENCE OF APOPTOTIC DELETION OF AUTOREACTIVE T-CELLS IN THE CENTRAL-NERVOUS-SYSTEM

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis r ats by the i.v, injection of 10(7) cloned V(beta)8.2(+) T cells specif ic for the 72-89 peptide of guinea pig myelin basic protein (MBP). Som e animals were injected simultaneously with 10(7) cloned T cells speci fic for ovalbumin (OVA), Lymphocytes were isolated from the spinal cor d and from the peripheral lymphoid organs of these rats and the freque ncies of MBP-peptide-specific or OVA-specific proliferating cells were estimated by limiting dilution analysis at different times after cell transfer, The frequencies of cells specific for MBP(72-89) or OVA in the spinal cord were highest 5 days after cell transfer (MBP(72-88), 1 in 1149; OVA, 1 in 1116). On day 7, when the rats were recovering, th e frequency of cells specific for MBP(72-89) in the spinal cord fell d ramatically to <1 in 10(5), while that of OVA-specific cells decreased to a much lesser extent(1 in 7001). The frequencies of MBP(72-89)-spe cific cells in the peripheral lymphoid organs during and after recover y were also much lower than those of OVA-specific cells. A similar pat tern of down-regulation of the MBP-peptide-specific, but not the OVA-s pecific, T cell response was observed in the spleen and mesenteric lym ph nodes (MLN) of rats 38 days after the active induction of EAE by im munization with equal amounts of MBP and OVA in adjuvants, In the pass ively transferred model, cells isolated from the spinal cord and MLN o n day 7 did not regain responsiveness to MBP(72-89) after incubation w ith high levels of IL-2, indicating that the unresponsiveness was not due to T cell anergy. Thus this study demonstrates that there is a spe cific down-regulation of the MBP(72-89)-specific T cell response durin g spontaneous recovery from EAE, This conclusion is consistent with ou r previous observation that V(beta)8.2(+) T cells are selectively elim inated from the CNS by apoptosis during recovery from EAE induced by t he passive transfer of V(beta)8.2(+) T cells reactive to this MBP pept ide. In contrast to autoreactive T cells, the non-autoreactive T cells that accumulate in the CNS during EAE appear to recirculate to the pe ripheral lymphoid organs.