T-CELL RECEPTOR V-BETA GENE USAGE IN THE RECOGNITION OF MYELIN BASIC-PROTEIN BY CEREBROSPINAL FLUID-DERIVED AND BLOOD-DERIVED T-CELLS FROM PATIENTS WITH MULTIPLE-SCLEROSIS

Because of its proximity to the central nervous system, the cerebrospi nal fluid (CSF) represents an important source of T cells that potenti ally could mediate putative autoimmune diseases such as multiple scler osis (MS). To overcome the low CSF cellularity, we evaluated culture c onditions that could expand CSF T cells, with a focus on the expressio n of T-cell receptor V beta genes utilized by T cells specific for the potentially encephalitogenic autoantigen myelin basic protein (BP). E xpansion of ''activated'' CSF cells with IL-2/IL-4 plus accessory cell s optimally retained BP-responsive T cells that over-expressed V beta 1, V beta 2, V beta 5, or V beta 18, compared to expansion using super natants from PHA-stimulated blood cells, or anti-CD3 antibody that led to different V gene bias and rare reactivity to BP. Sequential evalua tion of paired CSF and blood samples from a relapsing remitting MS pat ient indicated that BP-reactive T cells were present in CSF during the period of clinical activity, and the pattern of BP recognition in CSF was partially reflected in blood, even after CSF reactivity had dissi pated during remission. Over-expressed V beta genes were not always co nstant, however, since in three sequential evaluations of a chronic pr ogressive MS patient, V beta genes over-expressed in the first BP-reac tive CSF switched to a different V beta gene bias that was present in the second and third CSF samples. Blood samples reflected each pattern of CSF V beta gene bias, but retained the initial bias for at least 4 months after its disappearance from CSF. These data indicate that sel ective expansion of IL-2/IL-4-responsive CSF cells favors growth of th e BP-reactive subpopulation, and, in a limited number of patients stud ied, reflected clinical disease activity. In comparison, blood T cells provided a partial but longer lasting reflection of the CSF BP reacti vity and V beta gene bias. (C) 1994 Wiley-Liss, Inc.