Multiple Sclerosis: Limited Diversity of the Vδ2‐Jδ3 T‐Cell Receptor in Chronic Active Lesions

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Abstract
T lymphocytes bearing the γδ T‐cell receptor have been found in the central nervous system of patients with multiple sclerosis in association with demyelinated lesions. Although the biological function of these cells remains to be established, it has been proposed that they are involved in the response to highly conserved antigens, such as heat shock proteins (hsp), expressed during tissue damage and thus may contribute to the development of an autoimmune response. Using polymerase chain reaction, we probed for the presence of T‐cell receptor γδ cells in fresh‐frozen early autopsy brain tissue from patients with multiple sclerosis and patients with non‐multiple sclerosis conditions. The results demonstrated the presence of two major V‐J combinations of the T‐cell receptor δ chain–Vδ2‐Jδ3, Vδ2‐Jδ1– and we used a direct sequencing technique to determine whether this γδ T‐cell population was clonal or diverse. In chronic‐active plaques from 9 patients with multiple sclerosis, we found a striking predominant gene rearrangement within the Vδ2‐Jδ3 T‐cell receptor population that was not present in central nervous system tissue from patients with other neurological diseases. In contrast, within the Vδ2‐Jδ1 T‐cell receptor population, a predominant rearrangement pattern was detected in only 1 of the multiple sclerosis patients. The sequence of the predominant Vδ2‐Jδ3 gene rearrangement was confirmed by cloning and sequencing the gene products from 1 multiple sclerosis patient. This junctional region was characterized by shortened Dδ and Jδ segments, few N region insertions, and use of the third reading frame of the Dδ3 segment. These data strongly support the conclusion that within chronic‐active multiple sclerosis lesions, T cells bearing the Vδ2‐Dδ3‐Jδ3 receptor might have arisen as a response to a common antigen.