title: Expression of CD1d molecules by human schwann cells and potential interactions with immunoregulatory invariant NK T cells.
abstract: CD1d-restricted NKT cells expressing invariant TCR alpha-chains (iNKT cells) produce both proinflammatory and anti-inflammatory cytokines rapidly upon activation, and are believed to play an important role in both host defense and immunoregulation. To address the potential implications of iNKT cell responses for infectious or inflammatory diseases of the nervous system, we investigated the expression of CD1d in human peripheral nerve. We found that CD1d was expressed on the surface of Schwann cells in situ and on primary or immortalized Schwann cell lines in culture. Schwann cells activated iNKT cells in a CD1d-dependent manner in the presence of alpha-galactosylceramide. Surprisingly, the cytokine production of iNKT cells stimulated by alpha-galactosylceramide presented by CD1d+ Schwann cells showed a predominance of Th2-associated cytokines such as IL-5 and IL-13 with a marked deficiency of proinflammatory Th1 cytokines such as IFN-gamma or TNF-alpha. Our findings suggest a mechanism by which iNKT cells may restrain inflammatory responses in peripheral nerves, and raise the possibility that the expression of CD1d by Schwann cells could be relevant in the pathogenesis of infectious and inflammatory diseases of the peripheral nervous system.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Jin S
authors.initials: JS
authors.lastname: Im
authors.forename: Nikos
authors.initials: N
authors.lastname: Tapinos
authors.forename: Gue-Tae
authors.initials: GT
authors.lastname: Chae
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: George H
authors.initials: GH
authors.lastname: DeVries
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Anura
authors.initials: A
authors.lastname: Rambukkana
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D018949:Antigens, CD1 / Q000032:analysis*; D055610:Antigens, CD1d; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007109:Immunity; D007249:Inflammation; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology; D012583:Schwann Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide