title: Expression of CCR7 in multiple sclerosis: implications for CNS immunity.
abstract: It is unclear how immune cells traffic between the lymphoid compartment and the central nervous system (CNS), which lacks lymphatic vessels and is shielded by the blood-brain barrier. We studied the expression of CCR7, a chemokine receptor required for migration of T cells and dendritic cells (DCs) to lymphoid organs, in the CNS of patients with multiple sclerosis (MS) to gain insight into pathways for CNS immune cell trafficking. Inflamed MS lesions contained numerous CCR7+ myeloid cells expressing major histocompatibility complex class II, CD68 and CD86, consistent with maturing DCs. CCR7+ DCs also were identified in cerebrospinal fluid (CSF). These observations suggested that the afferent limb of CNS immunity is comprised, in part, of DCs, which are generated within the CNS and migrate to deep cervical lymph nodes through the CSF after antigen capture. Ninety percent of CSF T cells expressed CCR7 and CSF from patients with MS was relatively depleted of CCR7-negative effector-memory T cells. In contrast, all T cells in parenchymal MS lesions lacked CCR7, indicating local retention and differentiation of central-memory T cells upon restimulation by antigen within the CNS. These data suggested that the efferent limb of CNS immunity is executed by central-memory T cells, which enter CSF directly from the circulation.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Pia
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahad
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Callahan
authors.forename: Keith
authors.initials: K
authors.lastname: Sikora
authors.forename: Corinna
authors.initials: C
authors.lastname: Trebst
authors.forename: Barbara
authors.initials: B
authors.lastname: Tucky
authors.forename: Jerome
authors.initials: J
authors.lastname: Wujek
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Susan M
authors.initials: SM
authors.lastname: Staugaitis
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology; D007223:Infant; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine