Autoimmune CD4⁺ T cell memory: Lifelong persistence of encephalitogenic T cell clones in healthy immune repertoires

We embedded green fluorescent CD4⁺ T cells specific for myelin basic protein (MBP) (T_MBP-GFP cells) in the immune system of syngeneic neonatal rats. These cells persisted in the animals for the entire observation period spanning >2 years without affecting the health of the hosts. They maintained a memory phenotype with low levels of L-selectin and CD45RC, but high CD44. Although persisting in low numbers (0.01-0.1% of lymph node cells) they were sufficient to raise susceptibility toward clinical autoimmune disease. Immunization with MBP in IFA induced CNS inflammation and overt clinical disease in animals carrying neonatally transferred T _MBP-GFP cells, but not in controls. The onset of the clinical disease coincided with mass infiltration of T_MBP-GFP cells into the CNS. In the periphery, following the amplification phase a rapid contraction of the T cell population was observed. However, elevated numbers of fully reactive T _MBP-GFP cells remained in the peripheral immune system after acute experimental autoimmune encephalomyelitis mediating reimmunization-induced disease relapses.