Frequencies of neuroantigen-specific T cells in the central nervous system versus the immune periphery during the course of experimental allergic encephalomyelitis.
Direct measurements of the frequency and the cytokine signature of the neuroantigen-specific effector cells in experimental allergic encephalomyelitis (EAE) are a continuing challenge. This is true for lymphoid tissues, and more importantly, for the CNS itself. Using enzyme-linked immunospot analysis (ELISPOT) assays, we followed proteolipid protein (PLP) 139--151-specific T cells engaged by active immunization of SJL mice. The total numbers of PLP(139--151)-specific CD4 cells were highest before disease onset. At this time, these cells resided in lymphoid and nonlymphoid tissues, but were not detected in the CNS. While the PLP(139--151)-specific cells reached high frequencies in the CNS during clinical EAE, in absolute numbers, less than 20% of them were present in the target organ, with the majority residing in the periphery throughout all stages of the disease. The numbers of PLP(139--151)-specific cells gradually declined in both compartments with time. While eventually this first wave of effector cells completely disappeared from the CNS, PLP(178--191)-specific cells became engaged, being detected first in the CNS. These data suggest that throughout all stages of EAE, the effector cells in the CNS are recruited from a vast peripheral reservoir, and that the second wave of effector cells is engaged while the first wave undergoes exhaustion.
Targoni
O S
OS
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Baus
J
J
Hofstetter
H H
HH
Hesse
M D
MD
Karulin
A Y
AY
Boehm
B O
BO
Forsthuber
T G
TG
Lehmann
P V
PV
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014611:Vaccination
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)