T cell receptor γδ repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen-reactive γδ clones
✍ Scribed by Sabine Nick; Piero Pileri; Stefania Tongiani; Yasushi Uematsu; Ludwig Kappos; Gennaro De Libero
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 980 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
T cell receptor y6 repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen-reactive y6 clones
To study the relevance of y6 T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) y6 repertoire and the antigen reactivity of y6 clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of Val+ cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with Vy-and V6-specific monoclonal antibodies (mAb) showed that the V61 chain is most frequently associated with y chains belonging to theVyI family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both 6 and y genes indicating polyclonal expansion. y6 clones were established and some recognized glioblastoma, astrocytoma or monocytic cell lines. Stimulation with these targets induced serine esterase release and lymphokine expression characteristic of the THO-like phenotype. Remarkably, these tumor-reactive y6 cells were not detected in the peripheral blood using PCR oligotyping, but were found in other CSF lines independently established from the same MS patient. Altogether, these results demonstrate that in the CSF there is a skewed TCRy6 repertoire and suggest that y6 cells reacting against brain-derived antigens might have been locally expanded.