In:
Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 4 ( 1998-10), p. 1146-1150
Abstract:
Objective: To analyze the T-cell receptor (TCR) repertoire in the inflammatory infiltrates of the nervous system and tumor of patients with anti-Hu associated paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). Background: In PEM/SN, the pathogenic role of the infiltrating T cells is speculative. TCR analysis may establish whether these lymphocytes are attracted nonspecifically by a proinflammatory environment or are driven by a specific antigen or superantigen. Methods: We examined frozen tissues of seven patients with PEM/SN using immunohistochemical and PCR analysis. Of 62 tissue blocks from seven patients, 19 blocks from five patients had 〉 100 CD3+ cells per section infiltrating the nervous system or tumor. These infiltrates allowed screening of the TCR Vβ family repertoire using a panel of 18 antibodies that recognize family-specific regions of most TCR Vβ families against which antibodies have been generated. To distinguish between antigen-driven clonal and superantigen-driven family expansion, we extracted RNA from frozen tissue and performed reverse transcriptase (RT)-PCR analysis followed by subcloning and sequencing of the antigen-specific CDR3 region of the TCR Vβ chain. Results: All five patients showed a limited Vβ repertoire. An overrepresentation ( 〉 10% of total CD3+) of certain Vβ families was identified in three patients (as high as 45% of total CD3+), which consisted mainly of CD8+ cells. CDR3 sequences obtained from one patient revealed an in situ expansion of two clones in the amygdala (one at a frequency of 57%) and four clones in the tumor. Conclusion: These findings suggest that an antigen-driven oligoclonal cytotoxic T-cell response plays a role in the pathogenesis of anti-Hu associated PEM/SN.
Type of Medium:
Online Resource
ISSN:
0028-3878
,
1526-632X
DOI:
10.1212/WNL.51.4.1146
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1998
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