Cerebrospinal fluid γδ T cell frequency is age-related: a case control study of 435 children with inflammatory and non-inflammatory neurologic disorders

Summary

Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, especially due to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in pediatric neuroinflammation, we immunophenotyped CSF and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurologic disorders (NIND), 312 with opsoclonus-myoclonus (OMS), and 23 with other inflammatory neurologic disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency 27% in infants, 3.3% in teens. Inter-individual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation (HLA-DR), maturation (CD45RA, CD45RO), or intracellular cytokine staining (IL-4, IFN-γ) failed to discriminate OMS and NIND groups. Of 7 OMS immunotherapies/combinations, none significantly altered the frequency of total CSF γδ T cells or subsets. In OIND, the CSF γδ T cell frequency was <10% for single samples of other paraneoplastic disorders (ANNA-1, ANNA-2, teratoma-associated syndrome), cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis, and encephalitis. This study provides new insights into CSF γδ T cells in the pediatric population. Though their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy, and our age cut-off references for NIND are important findings for the design of future pediatric studies. This article is protected by copyright. All rights reserved.