Brain, Vol. 126, No. 1, 20-31, January 2002
Paolo A. Muraro*,1, Klaus-Peter Wandinger*,1, Bibiana Bielekova1, Bruno Gran1, Adriana Marques3, Ursula Utz2, Henry F. McFarland1, Steve Jacobson1 and Roland Martin1
1 Neuroimmunology Branch, 2 Neuroscience Center, National Institute of Neurological Disorders and Stroke, 3 Laboratory of Clinical Investigation, National Institute of Allergy Infectious Diseases, National Institutes of Health, MD, USA
T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases.
Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology.
Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis.
We developed and applied a highly specific and sensitive technique to track single CD4+ and CD8+ T cell clones through the detection and quantification of T cell receptor (TCR) a or ß chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)–PCR.
We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease.
Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both.
By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP.
T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders.
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