Clonal expansion and decreased occurence of peripheral blood γδ T cells of the Vδ2Jδ3 lineage in multiple sclerosis patients

Abstract

γδ T cells are implicated in autoimmune diseases but their precise function remains unclear. In multiple sclerosis (MS) brain tissue, γδ T cells co-localize with heat shock protein (hsp)65+ oligodendrocytes and are oligoclonally restricted in the Vδ2Jδ3 lineage. To investigate the homing properties and the degree of heterogeneity of Vδ2Jδ3 + γδ T cells in MS, peripheral blood lymphocytes (PBL) from 34 MS patients, 42 controls (14 autoimmune control patients, 28 healthy volunteers), and 11 lymphatic tissues of MS patients and controls were studied by PT-PCR and sequencing. Vδ2Jδ3 TCR rearrangement was detected in 27 out of 28 healthy controls, and was significantly less frequent in MS patients (24 out of 34) and autoimmune control patients (seven out of 14). It was present only in five out of 11 tissue specimens, none of them from MS patients. Direct sequencing and cloning/automated sequencing of the Vδ2Jδ3 PCR products indicated heterogeneity in healthy controls and oligoclonality in MS patients, but also in autoimmune control patients. Differences between MS patients and healthy controls were more accentuated in exacerbating hospitalized patients than in clinically stable outpatients participating in a clinical trial. Only one Vδ2Jδ3 sequence of a total of 85 different sequences obtained was shared between two MS patients. Taken together, evidence for clonal expansion of Vδ2Jδ3 + γδ T cells was found in PBL of MS patients. This T cell subset, previously shown to be present in 100% of chronic-active MS plaques, might home to the CNS in MS, resulting in its under-representation in the blood.