Abstract
BackgroundCirculating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors. We reasoned that a bias (either enrichment or depletion) of CSF T cell expression of known organ-specific trafficking determinants might suggest that homing of T cells to the subarachnoid space could be governed by a CNS-specific adhesion molecule or chemokine receptor.ResultsThe expression of cutaneous leukocyte antigen (CLA) and CC-chemokine receptor 4 (CCR4; associated with skin-homing) as well as the expression of integrin α4β7 and CCR9 (associated with gut-homing) was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry. CSF contained similar proportions of CD4+ memory T cells expressing CLA, CCR4, integrin α4β7 and CCR9 as paired blood samples.ConclusionThe results extend our previous findings that antigen-experienced CD4+ memory T cells traffic through the CSF in proportion to their abundance in the peripheral circulation. Furthermore, the ready access of skin- and gut-homing CD4+ memory T cells to the CNS compartment via CSF has implications for the mechanisms of action of immunotherapeutic strategies, such as oral tolerance or therapeutic immunization, where immunogens are administered using an oral or subcutaneous route.
Highlights
Circulating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors
In this study we addressed the expression of trafficking determinants known to be involved in organ-specific trafficking to the skin (CLA and chemokine receptor 4 (CCR4)) and the small intestines on CSF T cells from patients with non-inflammatory neurological diseases (NIND)
CD4+ memory T cells expressing cutaneous leukocyte antigen (CLA) and integrin α4β7 are present in the CSF Flow cytometry was used to determine the expression of CLA and integrin α4β7, two adhesion molecules involved in the selective recruitment of T cells to the skin and gut, respectively, on T cells in paired blood and CSF samples from four NIND patients
Summary
Circulating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors. The differentiation of naïve T cells into an activated memory phenotype is characterized by an extensive change in the expression of trafficking determinants, resulting in the acquisition of homing receptors that enable the cells to migrate from the circulation into peripheral tissues. This change in T cell homing potential is affected by the microenvironment where initial antigen recognition occurred,. Circulating T cells can be divided into tissue specific subsets, each of which have the ability to traffic through certain tissue compartments, but which are excluded from others
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