Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins.
Open Access
- 1 April 1992
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 175 (4), 1055-1066
- https://doi.org/10.1084/jem.175.4.1055
Abstract
Natural killer (NK) cells have been defined as CD3 epsilon-, CD16+ and/or CD56+ lymphocytes that mediate major histocompatibility complex (MHC)-unrestricted cytotoxicity against certain tumors and virus-infected cells. Unlike T lymphocytes, NK cells do not rearrange or productively express T cell antigen receptor genes. Moreover, NK cells from adults have been reported to not express CD3 gamma, delta, or epsilon proteins on the cell surface or in the cytoplasm. Nonetheless, NK cells have been shown to share a number of antigenic and functional similarities to T cells that suggest the possibility of common origins. In this report, we demonstrate that functional NK cells exist in liver at early stages of human embryonic development. Freshly isolated fetal NK cells mediated MHC-unrestricted cytotoxicity against NK-sensitive targets and acquired the ability to lyse NK-resistant tumors after overnight culture in interleukin 2. Unlike adult NK cells, freshly isolated fetal liver NK cells and clones derived from these cells, as well as a subset of cord blood NK cells, express substantial levels of CD3 delta and CD3 epsilon proteins in the cytoplasm. Expression of CD3 epsilon and CD3 delta transcripts and cytoplasmic proteins in fetal NK clones was confirmed by polymerase chain reaction and Western blot analysis. These findings support the concept that NK and T cells may arise from a common progenitor that expresses components of the CD3 complex. Alternatively, it is possible that the cytoplasmic CD3 delta, epsilon+ fetal NK cells represent a distinct subpopulation of NK cells that is predominant in the fetus, but replaced by the cytoplasmic CD3 delta,epsilon- adult NK cell population after embryogenesis.Keywords
This publication has 41 references indexed in Scilit:
- Identification of a novel human thymocyte subset with a phenotype of CD3- CD4+ CD8 alpha + beta-1. Possible progeny of the CD3- CD4- CD8- subset.The Journal of Immunology, 1991
- Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry.1991
- Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 δ and ε but not membrane CD3International Immunology, 1991
- A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production.The Journal of Experimental Medicine, 1990
- Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells.Proceedings of the National Academy of Sciences of the United States of America, 1990
- The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer.The Journal of Experimental Medicine, 1987
- Human bone marrow cells positive for terminal deoxynucleotidyl transferase (TdT), HLA-DR, and a T cell marker may represent prothymocytes.The Journal of Immunology, 1985
- The T3/T cell receptor complex: antigenic distinction between the two 20-kd T3 (T3-delta and T3-epsilon) subunits.1985
- Development of natural killer cell function in the human fetus.The Journal of Immunology, 1983
- Isolation of biologically active ribonucleic acid from sources enriched in ribonucleaseBiochemistry, 1979