TCR peptide therapy decreases the frequency of encephalitogenic T cells in the periphery and the central nervous system

Arthur Vandenbark, Margarita Vainiene, Bozena Celnik, George Hashim, Halina Offner

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The Vβ8 CDR2 consensus peptide, residues 44-54, is highly effective in the treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To monitor immunological changes during EAE resulting from TCR peptide therapy, the frequencies of encephalitogenic and regulatory T cells were quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells specific for basic protein and its major encephalitogenic epitope, residues 72-89, increased during EAE to about 1 cell per 100 000 lymph node or blood cells at the peak of clinical disease, and then declined. In contrast, the frequency of these T cells in spinal cord was highest, 50 per 100 000, prior to onset of clinical signs, and then decreased rapidly prior to spontaneous recovery. Injection of 100 μg of TCR Vβ8-44-54 peptide caused a decrease within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89-reactive T cells in blood and spinal cord, and in the total number of infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP increased, suggesting epitope switching at the site of GP-BP immunization. Conversely, the frequency of T cells specific for the Vβ8-44-54 peptide increased, especially in blood and spinal cord, whereas T cell frequencies to control antigens were unchanged. These data document the critical presence of encephalitogenic T cells within the spinal cord during clinical EAE, and demonstrate that rapid and profound changes in T cell frequencies in the periphery and spinal cord are triggered by TCR peptide therapy.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalJournal of Neuroimmunology
Volume39
Issue number3
DOIs
StatePublished - 1992

Fingerprint

Central Nervous System
T-Lymphocytes
Spinal Cord
Peptides
Autoimmune Experimental Encephalomyelitis
Epitopes
Guinea Pigs
Therapeutics
Lymph Nodes
Proteins
Regulatory T-Lymphocytes
Immunization
Blood Cells
Cell Count
Antigens
Injections

Keywords

  • Experimental autoimmune encephalomyelitis
  • Myelin basic protein
  • T cell frequency
  • TCR peptide therapy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

Cite this

TCR peptide therapy decreases the frequency of encephalitogenic T cells in the periphery and the central nervous system. / Vandenbark, Arthur; Vainiene, Margarita; Celnik, Bozena; Hashim, George; Offner, Halina.

In: Journal of Neuroimmunology, Vol. 39, No. 3, 1992, p. 251-260.

Research output: Contribution to journalArticle

@article{a5f554ec885240849d63bb8efc5cae45,
title = "TCR peptide therapy decreases the frequency of encephalitogenic T cells in the periphery and the central nervous system",
abstract = "The Vβ8 CDR2 consensus peptide, residues 44-54, is highly effective in the treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To monitor immunological changes during EAE resulting from TCR peptide therapy, the frequencies of encephalitogenic and regulatory T cells were quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells specific for basic protein and its major encephalitogenic epitope, residues 72-89, increased during EAE to about 1 cell per 100 000 lymph node or blood cells at the peak of clinical disease, and then declined. In contrast, the frequency of these T cells in spinal cord was highest, 50 per 100 000, prior to onset of clinical signs, and then decreased rapidly prior to spontaneous recovery. Injection of 100 μg of TCR Vβ8-44-54 peptide caused a decrease within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89-reactive T cells in blood and spinal cord, and in the total number of infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP increased, suggesting epitope switching at the site of GP-BP immunization. Conversely, the frequency of T cells specific for the Vβ8-44-54 peptide increased, especially in blood and spinal cord, whereas T cell frequencies to control antigens were unchanged. These data document the critical presence of encephalitogenic T cells within the spinal cord during clinical EAE, and demonstrate that rapid and profound changes in T cell frequencies in the periphery and spinal cord are triggered by TCR peptide therapy.",
keywords = "Experimental autoimmune encephalomyelitis, Myelin basic protein, T cell frequency, TCR peptide therapy",
author = "Arthur Vandenbark and Margarita Vainiene and Bozena Celnik and George Hashim and Halina Offner",
year = "1992",
doi = "10.1016/0165-5728(92)90259-N",
language = "English (US)",
volume = "39",
pages = "251--260",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - TCR peptide therapy decreases the frequency of encephalitogenic T cells in the periphery and the central nervous system

AU - Vandenbark, Arthur

AU - Vainiene, Margarita

AU - Celnik, Bozena

AU - Hashim, George

AU - Offner, Halina

PY - 1992

Y1 - 1992

N2 - The Vβ8 CDR2 consensus peptide, residues 44-54, is highly effective in the treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To monitor immunological changes during EAE resulting from TCR peptide therapy, the frequencies of encephalitogenic and regulatory T cells were quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells specific for basic protein and its major encephalitogenic epitope, residues 72-89, increased during EAE to about 1 cell per 100 000 lymph node or blood cells at the peak of clinical disease, and then declined. In contrast, the frequency of these T cells in spinal cord was highest, 50 per 100 000, prior to onset of clinical signs, and then decreased rapidly prior to spontaneous recovery. Injection of 100 μg of TCR Vβ8-44-54 peptide caused a decrease within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89-reactive T cells in blood and spinal cord, and in the total number of infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP increased, suggesting epitope switching at the site of GP-BP immunization. Conversely, the frequency of T cells specific for the Vβ8-44-54 peptide increased, especially in blood and spinal cord, whereas T cell frequencies to control antigens were unchanged. These data document the critical presence of encephalitogenic T cells within the spinal cord during clinical EAE, and demonstrate that rapid and profound changes in T cell frequencies in the periphery and spinal cord are triggered by TCR peptide therapy.

AB - The Vβ8 CDR2 consensus peptide, residues 44-54, is highly effective in the treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To monitor immunological changes during EAE resulting from TCR peptide therapy, the frequencies of encephalitogenic and regulatory T cells were quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells specific for basic protein and its major encephalitogenic epitope, residues 72-89, increased during EAE to about 1 cell per 100 000 lymph node or blood cells at the peak of clinical disease, and then declined. In contrast, the frequency of these T cells in spinal cord was highest, 50 per 100 000, prior to onset of clinical signs, and then decreased rapidly prior to spontaneous recovery. Injection of 100 μg of TCR Vβ8-44-54 peptide caused a decrease within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89-reactive T cells in blood and spinal cord, and in the total number of infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP increased, suggesting epitope switching at the site of GP-BP immunization. Conversely, the frequency of T cells specific for the Vβ8-44-54 peptide increased, especially in blood and spinal cord, whereas T cell frequencies to control antigens were unchanged. These data document the critical presence of encephalitogenic T cells within the spinal cord during clinical EAE, and demonstrate that rapid and profound changes in T cell frequencies in the periphery and spinal cord are triggered by TCR peptide therapy.

KW - Experimental autoimmune encephalomyelitis

KW - Myelin basic protein

KW - T cell frequency

KW - TCR peptide therapy

UR - http://www.scopus.com/inward/record.url?scp=0026653697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026653697&partnerID=8YFLogxK

U2 - 10.1016/0165-5728(92)90259-N

DO - 10.1016/0165-5728(92)90259-N

M3 - Article

VL - 39

SP - 251

EP - 260

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 3

ER -