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- Title
Ex vivo detection of myelin basic protein-reactive T cells in multiple sclerosis and controls using specific TCR oligonucleotide probes.
- Authors
Hong, Jian; Zang, Ying C. Q.; Li, Sufang; Rivera, Victor M.; Zhang, Jingwu Z.
- Abstract
T cell reactivity to candidate myelin autoantigens, such as myelin basic protein (MBP), may play an important role in the pathogenesis of multiple sclerosis (MS). Although MBP-reactive T cellshave been found to undergo in vivo activation in patients with MS, their true precursor frequency in MS is unknown as current frequency analysis is commonly based on the T cell functional responses to MBP. In this study, we developed a TCR sequence-based ex vivo detection system using colony hybridization with oligonucleotide probes specific for CDR3 of selected T cell clones for the analysis of true T cell precursor frequency in PBMC. The results revealed that the precursor frequency of five independent T cell clones recognizing the immunodominant MBP region was found to be in the range of 1.6×10 in total T cells in three HLA-DR2 patients with MS compared to that of 0.25×10 in HLA-DR2 healthy individuals. The observed frequency of MBP-reactive T cells in MS patients was considerably higher than those measured in parallel by cell culture-based analysis (2.3×10) or by enzyme-linked immunospot assay (3.9×10) in the same peripheral blood mononuclear cell specimens. Furthermore, the study showed that MBP-reactive T cells detected ex vivo belonged to CD45RA, CD25 and CD95 T cell subsets as evidenced by preferential expression of specific TCR transcripts in these cell fractions.
- Publication
European Journal of Immunology, 2004, Vol 34, Issue 3, p870
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200324790