Ror Gamma T Expression And Lymphoid Neogenesis In The Brain Of Patients With Secondary Progressive Multiple Sclerosis

Ectopic B-cell follicle-like structures (ELS) are found in the meninges of patients with secondary progressive multiple sclerosis (SPMS). Because cells expressing the transcriptional regulator retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) and producing interleukin 17 (IL17), e. g. T helper 17 cells and lymphoid tissue inducer (LTi) cells, have been implicated in the formation of ELS, we studied ROR gamma t and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS. By immunohistochemistry, small numbers of ROR gamma t-positive cells were detected in the meninges of 6 of 12 SPMS cases analyzed. ROR gamma t-positive cells were localized in B-cell follicles or aggregates and nearby diffuse meningeal infiltrates, and predominantly co-expressed CD3. Only a few ROR gamma t-positive, CD3-negative cells were observed, suggesting the presence of group 3 innate lymphoid cells, which comprise the LTi cell subset. Some IL17-positive cells, co-expressing in part ROR gamma t and predominantly CD3, were found in meningeal B-cell follicles from 4 SPMS cases. Rare ROR gamma t-positive and IL17-positive cells were detected in white matter. Gene expression analysis of laser dissected meningeal infiltrates and white matter lesions confirmed low frequencies and virtual absence of ROR gamma t and IL17 signals, respectively. Thus, there is selective migration or survival of ROR gamma t-positive cells in MS patient meninges and an association of these cells with ELS.