Enriched CD161highCCR6+γδ T Cells in the Cerebrospinal Fluid of Patients With Multiple Sclerosis

Abstract

Autoreactive helper T subtype 17 (T_H17) cells are important inducers of immunopathology in various animal models of organ-specific autoimmunity.¹ In addition, T_H17 cells appear to be enriched in the peripheral blood and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS).² However, T_H17-associated effector cytokines including interleukin 17A (IL-17A), IL-17F, IL-21, and IL-22 are also produced by γδ T cells.³ Based on a series of recent studies in murine model systems, it is believed that γδ T cells adopt distinct functional phenotypes according to the signature cytokines that they produce. Both the interferon-γ (IFN-γ)–producing (γδT1 cells) and IL-17–producing subset of γδ T cells (γδT17 cells) seem to be committed to their respective phenotype already during thymic development.⁴ Elevated fractions of T cells with a γδ T-cell receptor have been observed in blood samples of patients with MS and γδ T cells were found to occur in early MS lesions.^5-7 In human peripheral blood, γδ T cells compose only a small population of less than 5% of the entire CD3⁺ T-cell population. As opposed to CD4⁺ T_H and CD8⁺ cytotoxic T cells with conventional αβ T-cell receptors, γδ T cells are not HLA antigen restricted and are capable of responding rapidly to pattern recognition receptor signals as a first line of defense. Hence, γδ T cells are assumed to link innate with adaptive immune responses.⁸ It is possible that γδ T cells also play a role in lymphoid stress surveillance responses, implying their potential significance in tumor immunology and autoimmunity.⁹ However, it is unclear whether specific subsets of γδ T cells, ie, γδT1 vs γδT17 cells, are preferentially involved either in distinct autoimmune disorders or anatomical niches that are affected by these autoimmune disorders. Indeed, increased fractions of IL-17–producing γδ T cells have been recovered from the peripheral blood of patients with ankylosing spondylitis¹⁰ and from psoriasis lesions.¹¹