title: Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration.
abstract: Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37(-/-) mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37(-/-) mice coincides with a striking failure to induce antigen-specific IFN-γ-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo-tactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naïve T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37(-/-) mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37(-/-) mice is impaired DC migration.
authors: Department of Immunology, Monash University, Prahran, Victoria, Australia.
authors: Kate H
authors: KH
authors: Gartlan
authors: Janet L
authors: JL
authors: Wee
authors: Maria C
authors: MC
authors: Demaria
authors: Roza
authors: R
authors: Nastovska
authors: Tsz Man
authors: TM
authors: Chang
authors: Eleanor L
authors: EL
authors: Jones
authors: Vasso
authors: V
authors: Apostolopoulos
authors: Geoffrey A
authors: GA
authors: Pietersz
authors: Michael J
authors: MJ
authors: Hickey
authors: Annemiek B
authors: AB
authors: van Spriel
authors: Mark D
authors: MD
authors: Wright
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D059470:Tetraspanins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504565:Cd37 protein, mouse; D059470:Tetraspanins; D007371:Interferon-gamma