INCREASED FREQUENCY OF GAMMA-DELTA-T-CELLS IN CEREBROSPINAL-FLUID ANDPERIPHERAL-BLOOD OF PATIENTS WITH MULTIPLE-SCLEROSIS REACTIVITY, CYTOTOXICITY, AND T-CELL RECEPTOR-V GENE REARRANGEMENTS

Infiltrating gamma delta T cells are potentially involved in the centr al nervous system demyelination in multiple sclerosis (MS). To further study this hypothesis, we analyzed the frequency and functional prope rties of gamma delta T cells in peripheral blood (PB) and paired cereb rospinal fluid (CSF) of patients with MS and control subjects, includi ng patients with other neurologic diseases (OND) and healthy individua ls. The frequency analysis was performed under limiting dilution condi tion using rIL-2 and PHA. After PHA stimulation, a significantly incre ased frequency of gamma delta T cells was observed in PB (14.7 X 10(-4 )) and in CSF (15.8 x 10(-4)) of MS patients as compared with 4.3 x 10 (-4) in PB and 3.9 X 10(-4) detected in CSF of patients with OND. The frequency was represented equally in ND patients and normal individual s. Similarly, the IL-2-responsive gamma delta T cells occurred at a hi gher frequency in PB of MS (6.2 x 10(-4)) than in PB of control subjec ts (1.1 x 10(-4) in OND patients and 1.5 x 10(-4) in normal individual s). Forty-three percent (13 of 30) of the gamma delta T cell clones is olated from PB and CSF of MS patients responded to heat shock protein (HSP70) but not HSP65, whereas only 2 of 30 control gamma delta T cell clones reacted to the HSP. The majority of the gamma delta T cell clo nes were able to induce non-MHC-restricted cytolysis of Daudi cells. A ll clones displayed a substantial reactivity to bacterial superantigen s staphylococcal enterotoxin B and toxic shock syndrome toxin-1, irres pective of their gamma delta V gene usage. Furthermore, the gamma delt a T cell clones expressed predominantly TCRDV2 and CV2 genes (26 of 35 clones), whereas the clones derived from CSF of MS patients expressed either DV1 or DV2 genes. The obtained gamma delta clones, in general, represented rather heterogeneous clonal origins, even though a predom inant clonal origin was found in a set of 10 gamma delta clones derive d from one patient with MS. The present study provides new evidence su pporting a possible role of gamma delta T cells in the secondary infla mmatory processes in MS.