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.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
O S
OS
Targoni
J
J
Baus
H H
HH
Hofstetter
M D
MD
Hesse
A Y
AY
Karulin
B O
BO
Boehm
T G
TG
Forsthuber
P V
PV
Lehmann
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)