CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis

TY - JOUR

T1 - CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis

AU - Willing, Anne

AU - Leach, Oliver A

AU - Ufer, Friederike

AU - Attfield, Kathrine E

AU - Steinbach, Karin

AU - Kursawe, Nina

AU - Piedavent, Melanie

AU - Friese, Manuel A

N1 - © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) T cells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) T cells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8(+) MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8(+) MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8(+) T cells into the CNS. Notably, we were able to identify CD8(+) MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18-driven activation of CD8(+) MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8(+) MAIT-cell frequencies in the blood. Therefore, CD8(+) MAIT cells seem to play a role in the innate arm of immunopathology in MS.

AB - Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) T cells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) T cells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8(+) MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8(+) MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8(+) T cells into the CNS. Notably, we were able to identify CD8(+) MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18-driven activation of CD8(+) MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8(+) MAIT-cell frequencies in the blood. Therefore, CD8(+) MAIT cells seem to play a role in the innate arm of immunopathology in MS.

KW - CD8-Positive T-Lymphocytes

KW - Chemotaxis, Leukocyte

KW - Flow Cytometry

KW - Humans

KW - Immunohistochemistry

KW - Interleukin-18

KW - Lymphocyte Activation

KW - Multiple Sclerosis

KW - T-Lymphocyte Subsets

U2 - 10.1002/eji.201344160

DO - 10.1002/eji.201344160

M3 - SCORING: Journal article

C2 - 25043505

VL - 44

SP - 3119

EP - 3128

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 10

ER -