title: Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets.
abstract: Natural killer (NK) cells are known to reject MHC-mismatched targets within blood organs, yet their role in peripheral lymphoid tissue remains unresolved. Here we address the capacity of NK cells to migrate within lymph nodes (LN) using two-photon microscopy to characterize cell velocities and interaction dynamics within the native lymphoid-tissue environment. Adoptively transferred unmanipulated NK cells were highly motile (6-7 microm/min) and capable of forming transient contacts with both syngeneic and allogeneic B cells. Stable conjugate interactions (lasting >5 min) formed preferentially with allogeneic cells, resulting in diminished motility and subsequent elimination of the target cell. In marked contrast to unmanipulated cells, NK cells purified by CD49b-positive selection exhibited only limited motility (2-3 microm/min). This velocity impairment arose largely because CD49b cross-linking enhanced NK cell adhesion to collagen fibers within the node. Moreover, CD49b cross-linking prevented NK cells from reconstituting effector cytolytic function in vivo, inhibited target cell lysis in vitro, and augmented IFN-gamma responses to IL-2 activation in vitro. Taken together our data demonstrate that NK cells are a functionally important component of the LN microenvironment, and that cell motility and effector function are strongly modulated via CD49b manipulation.
authors.affiliation: Department of Physiology, University of California, Irvine, CA 92697-4561, USA.
authors.forename: Kym R
authors.initials: KR
authors.lastname: Garrod
authors.forename: Sindy H
authors.initials: SH
authors.lastname: Wei
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cahalan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology*; D039421:Integrin alpha2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D003432:Cross-Linking Reagents; D006649:Histocompatibility Antigens; D039421:Integrin alpha2