QUANTITATION OF T-CELL RECEPTOR V-BETA CHAIN EXPRESSION ON LYMPHOCYTES FROM BLOOD, BRAIN, AND SPINAL-FLUID IN PATIENTS WITH MULTIPLE-SCLEROSIS AND OTHER NEUROLOGICAL DISEASES

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system in which large numbers of T cells enter the brain and cerebrospinal fluid (CSF). To determine whether these cells represent restricted populations, we studied expression of T-cell receptor V-beta chains on paired samples from the central nervous system and blood of patients with MS or other neurological diseases (OND) using a quantitative polymerase chain reaction. The distribution of V-beta chain expression in blood was skewed, with a significant preponderance of message from V-beta genes 1 through 8 (p = 0.0001). Such skewing was not present in samples from the CSF and brain. Patterns of V-beta gene expression were different among paired samples from spinal fluid and blood and were relatively heterogeneous. Blood and CSF samples from a patient with acute meningitis were studied on two separate occasions. The patterns of V-beta expression changed over 72 hours in both the blood and the CSF. With one exception, no oligoclonal populations of T cells were observed nor were there disease-specific patterns of V-beta gene expression in the blood or CSF. Samples from 2 MS brains and 1 OND brain expressed patterns of V-beta genes that were different and less heterogeneous than those in paired blood. In addition, expression of V-beta 12 was remarkably increased in the 2 MS brains, suggesting a selective recruitment or expansion of T cells expressing this gene. These data demonstrate that populations of T cells from blood, spinal fluid, and brain differ from one another and can fluctuate during periods of acute inflammation. In addition, studies of brain T cells may be more informative in terms of defining oligoclonal populations of potentially pathogenic T cells than will studies of nonselected CSF T cells.