CEREBROSPINAL-FLUID OF MULTIPLE-SCLEROSIS PATIENTS - MOLECULAR AND FUNCTIONAL ANALYSES OF T-CELL RECEPTOR-GAMMA-DELTA REPERTOIRE IS SKEWED IN ANTIGEN-REACTIVE GAMMA-DELTA CLONES

被引:42
作者
NICK, S
PILERI, P
TONGIANI, S
UEMATSU, Y
KAPPOS, L
DELIBERO, G
机构
[1] UNIV BASEL HOSP,DEPT RES,CH-4031 BASEL,SWITZERLAND
[2] UNIV BASEL HOSP,NEUROL CLIN,CH-4031 BASEL,SWITZERLAND
关键词
T CELL RECEPTOR GAMMA-DELTA REPERTOIRE; MULTIPLE SCLEROSIS; CEREBROSPINAL FLUID CLONAL ANALYSIS;
D O I
10.1002/eji.1830250208
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To study the relevance of gamma delta T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) gamma delta repertoire and the antigen reactivity of gamma delta clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of V delta 1(+) cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with V gamma- and V delta-specific monoclonal antibodies (mAb) showed that the V delta 1 chain is most frequently associated with gamma chains belonging to the V gamma I family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both delta and gamma genes indicating polyclonal expansion. gamma delta 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 gamma delta 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 TCR gamma delta repertoire and suggest that gamma delta cells reacting against brain-derived antigens might have been locally expanded.
引用
收藏
页码:355 / 363
页数:9
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