CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis
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CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis. / Willing, Anne; Leach, Oliver A; Ufer, Friederike; Attfield, Kathrine E; Steinbach, Karin; Kursawe, Nina; Piedavent, Melanie; Friese, Manuel A.
In: EUR J IMMUNOL, Vol. 44, No. 10, 01.10.2014, p. 3119-28.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -