BIASED EXPRESSION OF T-CELL RECEPTOR GENES CHARACTERIZES ACTIVATED T-CELLS IN MULTIPLE-SCLEROSIS CEREBROSPINAL-FLUID

To better characterize the inflammatory response that occurs in the ne rvous system in multiple sclerosis (MS), T-cell receptor (TCR) gene ex pression was quantified from cerebrospinal fluid (CSF) cells of 21 pat ients with active disease, Unstimulated CSF cells expressed each of 22 different TCR beta chain variable region (V beta) gene families in pr oportion to their expression in simultaneously sampled peripheral bloo d. When CSF cells from individuals with MS were expanded by in vitro c ulture in T-cell growth factor/interleukin 2 and 4-containing medium ( TCGF/IL2/IL4), restricted numbers of V beta genes were expressed, In m any subjects, expanded CSF cells expressed predominantly V beta 2. In contrast to CSF, expansion of corresponding peripheral blood mononucle ar cells (PBMC) in TCGF/IL2/IL4 resulted in persistent expression of a ll Vn gene families, Within individuals, different V beta genes were o verexpressed by PBMC compared with CSF cells. No effect of the HLA hap lotype of the individual on CSF V beta gene expression was observed, E xpanded CSF cells retained their capacity to respond to mitogen stimul ation, but the proliferative response to myelin basic protein (MBP) wa s not enhanced. Finally, freshly obtained CSF cells stimulated directl y with MBP also expressed a limited number of V beta genes, although t hese were generally different from patterns observed following stimula tion with TCGF/IL2/IL4. Thus, restricted populations of T cells capabl e of responding to TCGF/IL2/IL4, presumably reflecting in vivo activat ed cells, are compartmentalized in the nervous system in MS. (C) 1996 Wiley-Liss, Inc.