Autoimmune CD4+ T Cell Memory: Lifelong Persistence of Encephalitogenic T Cell Clones in Healthy Immune Repertoires

Abstract

We embedded green fluorescent CD4+ T cells specific for myelin basic protein (MBP) (TMBP-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 TMBP-GFP cells, but not in controls. The onset of the clinical disease coincided with mass infiltration of TMBP-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 TMBP-GFP cells remained in the peripheral immune system after acute experimental autoimmune encephalomyelitis mediating reimmunization-induced disease relapses.

Lack of IL-15 results in the suboptimal priming of CD4+T cell response against an intracellular parasite

“…During the acute phase of the disease, CD4 ϩ T cells are the primary source of host IFN-␥ production (48), leading to immunopathology and ultimate death of the animal (11,26). CD4 ϩ T cells are known to play a primary role in number of autoimmune diseases such as inflammatory bowel disease, Crohn's disease, and experimental autoimmune encephalomyelitis (49)(50)(51). However, the importance of IL-15 in the elicitation of primary CD4 ϩ T cell response and subsequent effect on the pathogenesis of these diseases has not been reported.…”

Blood-borne soluble protein antigen intensifies T cell activation in autoimmune CNS lesions and exacerbates clinical disease

“…transfer of T OVA-GFP cells (2 ϫ 10 6 cells 5 days after stimulation with OVA-pulsed APCs, in 0.5 ml of Eagle's Hepes medium (per animal) into newborns as described (15). EAE was induced in 3-month-old T OVA-GFP memory animals by passive transfer of 5 ϫ 10 6 T MBP-RFP cell blasts.…”

“…In healthy animals, these brain-nonspecific memory T cells were excluded from the CNS tissue (SI Fig. 12A) (15). This scenario changed drastically after induction of adoptive transfer EAE by transferring redfluorescent-protein-labeled T MBP cells (T MBP-RFP cells).…”

Sequential polymicrobial infections lead to CNS inflammatory disease: Possible involvement of bystander activation in heterologous immunity

“…This time course is similar to what has been described in monophasic EAE, where acute CNS disease can be seen 2 weeks after EAE induction with complete remission by day 20. Kawakami et al (2005) demonstrated a rapid T cell contraction in the periphery after EAE induction. However, the authors showed lifelong persistence of encephalitogenic T cells that mediated EAE after a second EAE challenge.…”