title: CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph.
abstract: As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.
authors.affiliation: Istituto Giannina Gaslini, 16148 Genova, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Carrega
authors.forename: Irene
authors.initials: I
authors.lastname: Bonaccorsi
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.forename: Barbara
authors.initials: B
authors.lastname: Morandi
authors.forename: Petra
authors.initials: P
authors.lastname: Paul
authors.forename: Valeria
authors.initials: V
authors.lastname: Rizzello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cipollone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Navarra
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Guido
authors.initials: G
authors.lastname: Ferlazzo
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D020869:Gene Expression Profiling; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008196:Lymph; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D054353:Perforin / Q000378:metabolism*
chemical_list: D019002:CD56 Antigen; D018925:Chemokines; D054353:Perforin