Abstract
Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6+, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Video-Audio Media
MeSH terms
-
Adoptive Transfer
-
Animals
-
Autoimmunity* / drug effects
-
Brain / drug effects
-
Brain / immunology*
-
Brain / metabolism
-
Calcium Signaling
-
Cell Lineage*
-
Cerebrospinal Fluid / immunology
-
Cerebrospinal Fluid / metabolism
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Encephalomyelitis, Autoimmune, Experimental / metabolism
-
Fingolimod Hydrochloride / pharmacology
-
Gene Expression Profiling
-
Genes, T-Cell Receptor
-
HEK293 Cells
-
Humans
-
Immunosuppressive Agents / pharmacology
-
Intestines / drug effects
-
Intestines / immunology*
-
Intravital Microscopy
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Microscopy, Fluorescence
-
Multiple Sclerosis, Relapsing-Remitting / genetics
-
Multiple Sclerosis, Relapsing-Remitting / immunology
-
Multiple Sclerosis, Relapsing-Remitting / metabolism
-
Phenotype
-
Prospective Studies
-
RNA-Seq
-
Receptors, CXCR6 / genetics
-
Receptors, CXCR6 / metabolism
-
Receptors, Purinergic P2X7 / genetics
-
Receptors, Purinergic P2X7 / metabolism
-
Single-Cell Analysis
-
Skin / drug effects
-
Skin / immunology*
-
Skin / metabolism
-
T-Lymphocytes, Helper-Inducer / drug effects
-
T-Lymphocytes, Helper-Inducer / immunology*
-
T-Lymphocytes, Helper-Inducer / metabolism
-
T-Lymphocytes, Helper-Inducer / transplantation
-
Transcriptome
Substances
-
Cxcr6 protein, mouse
-
Immunosuppressive Agents
-
P2rx7 protein, mouse
-
Receptors, CXCR6
-
Receptors, Purinergic P2X7
-
Fingolimod Hydrochloride