Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions
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Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions. / Planas, Raquel; Metz, Imke; Ortiz, Yaneth; Vilarrasa, Nuria; Jelčić, Ilijas; Salinas-Riester, Gabriela; Heesen, Christoph; Brück, Wolfgang; Martin, Roland; Sospedra, Mireia.
In: ANN CLIN TRANSL NEUR, Vol. 2, No. 9, 09.2015, p. 875-93.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions
AU - Planas, Raquel
AU - Metz, Imke
AU - Ortiz, Yaneth
AU - Vilarrasa, Nuria
AU - Jelčić, Ilijas
AU - Salinas-Riester, Gabriela
AU - Heesen, Christoph
AU - Brück, Wolfgang
AU - Martin, Roland
AU - Sospedra, Mireia
PY - 2015/9
Y1 - 2015/9
N2 - OBJECTIVE: Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T cells in pattern II MS lesions.METHODS: We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them.RESULTS: We identified clonally expanded CD8(+) but also CD4(+) T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions.INTERPRETATION: Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients.
AB - OBJECTIVE: Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T cells in pattern II MS lesions.METHODS: We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them.RESULTS: We identified clonally expanded CD8(+) but also CD4(+) T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions.INTERPRETATION: Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients.
U2 - 10.1002/acn3.218
DO - 10.1002/acn3.218
M3 - SCORING: Journal article
C2 - 26401510
VL - 2
SP - 875
EP - 893
JO - ANN CLIN TRANSL NEUR
JF - ANN CLIN TRANSL NEUR
SN - 2328-9503
IS - 9
ER -