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.
Kawakami
Naoto
N
Department of Neuroimmunology, Max-Planck-Institute for Neurobiology, Martinsried, Germany.
Odoardi
Francesca
F
Ziemssen
Tjalf
T
Bradl
Monika
M
Ritter
Thomas
T
Neuhaus
Oliver
O
Lassmann
Hans
H
Wekerle
Hartmut
H
Flügel
Alexander
A
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