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T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression
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Journal Article
T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression
2022
Overview
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome. High frequency of CD4
+
FOXP3
−
effector T cells in blood and CSF is associated with poor survival, whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood are associated with better survival. Besides survival, phenotypic profiling of T cells could also predict disease progression rate. Single cell transcriptomics analysis of CSF samples shows clonally expanded CD4
+
and CD8
+
T cells in CSF, with characteristic gene expression patterns. In summary, T cell responses associate with and likely contribute to disease progression in ALS, supporting modulation of adaptive immunity as a viable therapeutic option.
Amyotrophic lateral sclerosis (ALS) is a primary neurodegenerative disease, which is characterized by increased immune cell infiltration of the central nervous system. Here authors show that the phenotypic profile of T cells in the blood and cerebrospinal fluid of newly diagnosed ALS patients can predict disease progression, thus providing evidence that T cells contribute to disease pathology.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/91
/ Amyotrophic lateral sclerosis
/ Amyotrophic Lateral Sclerosis - diagnosis
/ Amyotrophic Lateral Sclerosis - genetics
/ Amyotrophic Lateral Sclerosis - pathology
/ Blood
/ CD8-Positive T-Lymphocytes - pathology
/ Humanities and Social Sciences
/ Humans
/ Neurodegenerative Diseases - metabolism
/ Science
/ Survival
