CD11b and CD27 reflect distinct population and functional specialization in human natural killer cells

The identification of developmental stages in natural killer (NK) cells, especially in human NK cells, has lagged for decades. We characterize four novel populations defined by CD11b and CD27, which can represent the distinct stages of human NK cells from different tissues. Nearly all NK cells from peripheral blood are CD11b+ CD27− populations whereas NK cells from cord blood have CD11b+ CD27− and CD11b+ CD27+ populations. Interestingly, we have found large CD11b− CD27− populations of NK cells from deciduas. We also demonstrate that each population could be characterized by unique functional and phenotypic attributes. CD11b− CD27− NK cells display an immature phenotype and potential for differentiation. CD11b− CD27+ and CD11b+ CD27+ NK cells show the best ability to secrete cytokines. CD11b+ CD27− NK cells exhibit high cytolytic function. We demonstrate that human NK cells at different developmental stages have special functions and describe a new model of human NK cell differentiation.

[1]  M. Caligiuri,et al.  Immature NK Cells, Capable of Producing IL-22, Are Present in Human Uterine Mucosa , 2010, The Journal of Immunology.

[2]  P. Debré,et al.  NK Cell Terminal Differentiation: Correlated Stepwise Decrease of NKG2A and Acquisition of KIRs , 2010, PloS one.

[3]  P. Debré,et al.  Human NK cells display major phenotypic and functional changes over the life span , 2010, Aging cell.

[4]  M. Caligiuri,et al.  Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. , 2010, Immunity.

[5]  H. Spits,et al.  Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells , 2010, The Journal of experimental medicine.

[6]  C. Roth,et al.  Maturation of mouse NK cells is a 4-stage developmental program. , 2009, Blood.

[7]  M. Caligiuri,et al.  Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22. , 2009, Blood.

[8]  P. Brodin,et al.  NK cell education: not an on-off switch but a tunable rheostat. , 2009, Trends in immunology.

[9]  J. Lennerz,et al.  A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity , 2009, Nature.

[10]  P. Debré,et al.  Fully functional NK cells after unrelated cord blood transplantation , 2009, Leukemia.

[11]  P. Arck,et al.  The upside of natural killers , 2008, Nature Medicine.

[12]  M. Sormani,et al.  Temporal, quantitative, and functional characteristics of single-KIR-positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation. , 2008, Blood.

[13]  M. Robin,et al.  An Unusual CD56brightCD16low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation1 , 2008, The Journal of Immunology.

[14]  R. V. van Lier,et al.  CD27 Defines Phenotypically and Functionally Different Human NK Cell Subsets , 2008, The Journal of Immunology.

[15]  N. Huntington,et al.  Developmental pathways that generate natural-killer-cell diversity in mice and humans , 2007, Nature Reviews Immunology.

[16]  J. Hanna,et al.  When killers become helpers. , 2007, Trends in immunology.

[17]  A. Diefenbach,et al.  Dendritic cells prime natural killer cells by trans-presenting interleukin 15. , 2007, Immunity.

[18]  M. Caligiuri,et al.  Human natural killer cell development , 2006, Immunological reviews.

[19]  S. Nutt,et al.  Functional subsets of mouse natural killer cells , 2006, Immunological reviews.

[20]  L. Moretta,et al.  Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease. , 2006, Blood.

[21]  J. Hanna,et al.  Decidual NK cells regulate key developmental processes at the human fetal-maternal interface , 2006, Nature Medicine.

[22]  M. Caligiuri,et al.  Evidence for discrete stages of human natural killer cell differentiation in vivo , 2006, The Journal of experimental medicine.

[23]  M. Smyth,et al.  CD27 Dissects Mature NK Cells into Two Subsets with Distinct Responsiveness and Migratory Capacity1 , 2006, The Journal of Immunology.

[24]  P. Debré,et al.  NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. , 2005, Blood.

[25]  M. Caligiuri,et al.  A Novel Human CD34(+) Subset That Constitutively Expresses the High Affinity Interleukin-2 Receptor Traffics to Lymph Nodes and Differentiates into CD56Bright Natural Killer Cells. , 2004 .

[26]  L. Zitvogel,et al.  NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. , 2004, Blood.

[27]  P. Park,et al.  Human Decidual Natural Killer Cells Are a Unique NK Cell Subset with Immunomodulatory Potential , 2003, The Journal of experimental medicine.

[28]  M. Caligiuri,et al.  What does it take to make a natural killer? , 2003, Nature Reviews Immunology.

[29]  M. Caligiuri,et al.  CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. , 2003, Blood.

[30]  H. Petty,et al.  Function of the Lectin Domain of Mac-1/Complement Receptor Type 3 (CD11b/CD18) in Regulating Neutrophil Adhesion1 , 2002, The Journal of Immunology.

[31]  M. Caligiuri,et al.  The biology of human natural killer-cell subsets. , 2001, Trends in immunology.

[32]  K. Ando,et al.  Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells1 , 2001, The Journal of Immunology.

[33]  S. Hiby,et al.  Human Decidual Natural Killer Cells Express the Receptor for and Respond to the Cytokine Interleukin 151 , 2000, Biology of reproduction.

[34]  Y. W. Loke,et al.  Expression of killer cell inhibitory receptors on human uterine natural killer cells , 1997, European journal of immunology.

[35]  A. Galy,et al.  Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. , 1995, Immunity.

[36]  J. Miller,et al.  Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor. , 1994, Blood.

[37]  P. Anderson,et al.  Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing. , 1991, Journal of immunology.

[38]  L. Lanier,et al.  The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. , 1986, Journal of immunology.

[39]  G. Trinchieri,et al.  Human natural killer cells. , 1979, Transplantation proceedings.

[40]  P. Allavena,et al.  Regulation of adhesion and transendothelial migration of natural killer cells. , 1996, Natural immunity.

[41]  H. Nakauchi,et al.  Enrichment of interleukin-2-responsive natural killer progenitors in human bone marrow. , 1993, Blood.