title: Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis.
abstract: Whereas regulatory T (Treg) cells play an important role in the prevention of autoimmunity, increasing evidence suggests that their down-regulatory properties negatively affect immune responses directed against tumors. Treg cells selectively express chemokine receptors CCR4 and CCR8, and specific migration occurs following the release of various chemokines. Neoplastic meningitis (NM) resulting from leptomeningeal spread of systemic non-Hodgkin lymphoma (NHL) or carcinoma has a poor prognosis. We hypothesized that Treg-cell accumulation within the subarachnoid space as a result of interfering with tumor immunity may be relevant for survival of neoplastic cells. We collected cerebrospinal fluid (CSF) from 101 patients diagnosed with lymphomatous/carcinomatous NM and various inflammatory diseases (IDs) and noninflammatory neurologic disorders (NIDs). CSF Treg- cell counts were determined by flow cytometry, Treg cell-specific chemokines by enzyme-linked immunosorbent assay (ELISA), and Treg-cell trafficking by chemotaxis assay. Both frequencies of Treg-cell and Treg cell-specific chemotactic activities were significantly elevated in CSF samples of patients with NM. Local Treg-cell accumulation occurred without concomitant rise of conventional T (Tconv) cells, coincided with elevated concentrations of Treg cell-attracting chemokines CCL17 and CCL22 and correlated with numbers of atypical CSF cells. We conclude that Treg cells are specifically recruited into the CSF of patients with NM, suggesting that the presence of Treg cells within the subarachnoid space generates a microenvironment that may favor survival and growth of malignant cells.
authors.affiliation: Department of Neurology, University of Heidelberg, and Department of Neonatology, Children's Hospital, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.forename: Laila
authors.initials: L
authors.lastname: Schopp
authors.forename: Brigitte
authors.initials: B
authors.lastname: Storch-Hagenlocher
authors.forename: Benedikt
authors.initials: B
authors.lastname: Fritzsching
authors.forename: Christian
authors.initials: C
authors.lastname: Jacobi
authors.forename: Linda
authors.initials: L
authors.lastname: Milkova
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fritz
authors.forename: Alexander
authors.initials: A
authors.lastname: Schwarz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Suri-Payer
authors.forename: Manfred
authors.initials: M
authors.lastname: Hensel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D002470:Cell Survival / Q000276:immunology; D054414:Chemokine CCL17 / Q000134:cerebrospinal fluid / Q000276:immunology; D054422:Chemokine CCL22 / Q000134:cerebrospinal fluid / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D054398:Receptors, CCR4 / Q000276:immunology; D054401:Receptors, CCR8 / Q000276:immunology; D013346:Subarachnoid Space / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; C103330:CCR8 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054398:Receptors, CCR4; D054401:Receptors, CCR8