We characterized the T cells in NMOSD patients in detail in order to gain more insight into their possible influence on disease pathogenesis.

Neuromyelitis optica-spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system (CNS) that preferentially affects the optic nerve and spinal cord. The vast majority of patients (~75%) presents with autoantibodies against aquaporin 4 (AQP4), the predominant CNS water channel, which is abundantly expressed on astrocytes. The pathogenic AQP4 antibody as well as the B cells themselves are suggested to be a major driving force of the disease.  Nevertheless, the involvement of T cells in NMOSD pathogenesis is still not completely understood.

We performed an in-depth characterization of T cell subsets in the periphery and the cerebrospinal fluid (CSF) of NMOSD patients by multi-colour flow cytometry.

Samples from our treatment-naïve NMOSD cohort were compared with those from age- and sex matched healthy donors (HD) and treatment-naïve relapsing remitting MS (RRMS) patients. Furthermore, the T cell receptor (TCR) repertoire of CD4+ T cells and CD8+ T cells purified from peripheral blood, CSF and CNS tissue was analyzed by deep sequencing of the beta chain of the CDR3 region.

Flow cytometry revealed that naïve NMOSD patients displayed more activated and terminally differentiated T cells with features of increased cytotoxic capacity in the peripheral blood but also in the CSF as compared to RRMS patients as well as HDs.

TCR repertoires from NMOSD patients revealed a significantly increased clonality in the CD4 as well as in the CD8 compartment  indicating an antigen-driven expansion of distinct T cell clones. Furthermore, clonal expansion was also prominent in the CSF and in CNS tissue thus pointing towards a local antigen-driven process.

Taken together, our data suggest that T cells are involved in NMOSD disease pathogenesis, which needs to be further investigated.