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.
Department of Neuroimmunology, Max-Planck-Institute for Neurobiology, Martinsried, Germany.
Naoto
N
Kawakami
Francesca
F
Odoardi
Tjalf
T
Ziemssen
Monika
M
Bradl
Thomas
T
Ritter
Oliver
O
Neuhaus
Hans
H
Lassmann
Hartmut
H
Wekerle
Alexander
A
Flügel
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007114:Immunization; D007156:Immunologic Memory; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000235:genetics
D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins