Abstract
Purified CD3-4- thymocytes were obtained by depletion of CD3+ and CD4+ cells from fresh thymocyte suspensions. 5-15% of these cells were found to express CD16 antigen, while other natural killer (NK) cell markers were virtually absent. Double fluorescence analysis revealed that 20- 40% of thymic CD16+ cells coexpressed CD1, while approximately half were cyCD3+. When cultured in the presence of peripheral blood lymphocytes and H9 leukemia cell line as a source of irradiated feeder cells and interleukin 2 (IL-2), CD3-4- thymocytes underwent extensive proliferation. In addition, after 1-2 wk of culture, 30-50% of these cells were found to express CD16 surface antigen. Cloning under limiting dilution conditions of either CD3-4- or CD3-4-16- thymocytes in the presence of irradiated H9 cells resulted in large proportions (approximately 50%) of CD16+ clones. On the basis of the expression of surface CD16 and/or cyCD3 antigen, clones could be grouped in the following subsets: CD16+ cyCD3+; CD16+ cyCD3-; CD16- cyCD3+; and CD16- cyCD3-. All clones expressed CD56 surface antigen, displayed a strong cytolytic activity against NK sensitive (K562) and NK-resistant (M14) target cells, and produced IFN-gamma and tumor necrosis factor, but not IL-2. Similar to peripheral NK cells, thymic CD16+ cells expressed transcripts for CD16 and for CD3 epsilon (Biassoni, R., S. Ferrini, I. Prigione, A. Moretta, and E.O. Long, 1988. J. Immunol. 140:1685.) and zeta chains (Anderson, P., M. Caligiuri, J. Ritz, and S.F. Schlossman. 1989. Nature [Lond.]. 341:159). Therefore, it appears that cells that are phenotypically and functionally similar to CD3- CD16+ NK cells may arise from immature thymocytes.
Full Text
The Full Text of this article is available as a PDF (547.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson P., Caligiuri M., Ritz J., Schlossman S. F. CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex. Nature. 1989 Sep 14;341(6238):159–162. doi: 10.1038/341159a0. [DOI] [PubMed] [Google Scholar]
- Biassoni R., Ferrini S., Prigione I., Moretta A., Long E. O. CD3-negative lymphokine-activated cytotoxic cells express the CD3 epsilon gene. J Immunol. 1988 Mar 1;140(5):1685–1689. [PubMed] [Google Scholar]
- Blue M. L., Levine H., Daley J. F., Craig K. A., Schlossman S. F. Development of natural killer cells in human thymocyte culture: regulation by accessory cells. Eur J Immunol. 1987 May;17(5):669–673. doi: 10.1002/eji.1830170514. [DOI] [PubMed] [Google Scholar]
- Gold D. P., Puck J. M., Pettey C. L., Cho M., Coligan J., Woody J. N., Terhorst C. Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex. Nature. 1986 May 22;321(6068):431–434. doi: 10.1038/321431a0. [DOI] [PubMed] [Google Scholar]
- Haynes B. F., Denning S. M., Singer K. H., Kurtzberg J. Ontogeny of T-cell precursors: a model for the initial stages of human T-cell development. Immunol Today. 1989 Mar;10(3):87–91. doi: 10.1016/0167-5699(89)90232-6. [DOI] [PubMed] [Google Scholar]
- Krissansen G. W., Owen M. J., Verbi W., Crumpton M. J. Primary structure of the T3 gamma subunit of the T3/T cell antigen receptor complex deduced from cDNA sequences: evolution of the T3 gamma and delta subunits. EMBO J. 1986 Aug;5(8):1799–1808. doi: 10.1002/j.1460-2075.1986.tb04429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurtzberg J., Waldmann T. A., Davey M. P., Bigner S. H., Moore J. O., Hershfield M. S., Haynes B. F. CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells. Blood. 1989 Feb;73(2):381–390. [PubMed] [Google Scholar]
- Michon J. M., Caligiuri M. A., Hazanow S. M., Levine H., Schlossman S. F., Ritz J. Induction of natural killer effectors from human thymus with recombinant IL-2. J Immunol. 1988 May 15;140(10):3660–3667. [PubMed] [Google Scholar]
- Mingari M. C., Varese P., Bottino C., Melioli G., Moretta A., Moretta L. Clonal analysis of CD4-CD8- human thymocytes expressing a T cell receptor gamma/delta chain. Direct evidence for the de novo expression of CD8 surface antigen and of cytolytic activity against tumor targets. Eur J Immunol. 1988 Nov;18(11):1831–1834. doi: 10.1002/eji.1830181127. [DOI] [PubMed] [Google Scholar]
- Moretta A., Bottino C., Pende D., Tripodi G., Tambussi G., Viale O., Orengo A., Barbaresi M., Merli A., Ciccone E. Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition. J Exp Med. 1990 Dec 1;172(6):1589–1598. doi: 10.1084/jem.172.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moretta A., Pantaleo G., Moretta L., Cerottini J. C., Mingari M. C. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983 Feb 1;157(2):743–754. doi: 10.1084/jem.157.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poggi A., Biassoni R., Pella N., Paolieri F., Bellomo R., Bertolini A., Moretta L., Mingari M. C. In vitro expansion of CD3/TCR- human thymocyte populations that selectively lack CD3 delta gene expression: a phenotypic and functional analysis. J Exp Med. 1990 Nov 1;172(5):1409–1418. doi: 10.1084/jem.172.5.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ravetch J. V., Perussia B. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481–497. doi: 10.1084/jem.170.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Royer H. D., Ramarli D., Acuto O., Campen T. J., Reinherz E. L. Genes encoding the T-cell receptor alpha and beta subunits are transcribed in an ordered manner during intrathymic ontogeny. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5510–5514. doi: 10.1073/pnas.82.16.5510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Transy C., Moingeon P. E., Marshall B., Stebbins C., Reinherz E. L. Most anti-human CD3 monoclonal antibodies are directed to the CD3 epsilon subunit. Eur J Immunol. 1989 May;19(5):947–950. doi: 10.1002/eji.1830190525. [DOI] [PubMed] [Google Scholar]
- Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weissman A. M., Hou D., Orloff D. G., Modi W. S., Seuanez H., O'Brien S. J., Klausner R. D. Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9709–9713. doi: 10.1073/pnas.85.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]