Abstract
In the absence of antigenic or mitogenic stimulation, certain peripheral blood lymphocytes exhibit proliferative and lymphokine-activated killer (LAK) cell activities when cultured with recombinant IL-2. Both activities were found to be an exclusive property of lymphocytes expressing type 3 complement receptors (CR3) identified by anti-CD11 monoclonal antibodies. CD11+ lymphocytes were then fractionated into three subsets by two-color flow cytometry. These included CD16+ cells, which display distinctive Fc receptors for IgG (CD16). Using anti-CD5, the CD11+ CD16- lymphocytes were separated into non-T cell and T cell subsets. The two non-T cell subsets (CD11+ CD16+ and CD11+ CD16- CD5-), but not the T cell subset (CD11+ CD16- CD5+), could proliferate in response to IL-2. Both CD11+ non-T cell subsets, but not the CD11+ T cell subset, had the capacity to mediate natural killer cell activity. However, all three CD11+ lymphocyte subsets were capable of generating LAK activity. These findings are consistent with the concept that two signals are required to stimulate T cells to proliferate. However, at least a small subset of blood T cells can be activated by IL-2 to become LAK cells.
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Selected References
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- Abo W., Gray J. D., Bakke A. C., Horwitz D. A. Studies on human blood lymphocytes with iC3b (type 3) complement receptors. II. Characterization of subsets which regulate pokeweed mitogen-induced lymphocyte proliferation and immunoglobulin synthesis. Clin Exp Immunol. 1987 Mar;67(3):544–555. [PMC free article] [PubMed] [Google Scholar]
- Bakke A. C., Gray J. D., Abo W., Quismorio F. P., Jr, Lash A., Cooper S. M., Horwitz D. A. Studies on human blood lymphocytes with iC3b (type 3) complement receptors. I. Granular, Fc-IgG receptor positive and negative subsets in healthy subjects and patients with systemic lupus erythematosus. J Immunol. 1986 Feb 15;136(4):1253–1259. [PubMed] [Google Scholar]
- Bich-Thuy L. T., Lane H. C., Fauci A. S. Recombinant interleukin-2-induced polyclonal proliferation of in vitro unstimulated human peripheral blood lymphocytes. Cell Immunol. 1986 Apr 1;98(2):396–410. doi: 10.1016/0008-8749(86)90299-6. [DOI] [PubMed] [Google Scholar]
- Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Damle N. K., Doyle L. V., Bradley E. C. Interleukin 2-activated human killer cells are derived from phenotypically heterogeneous precursors. J Immunol. 1986 Nov 1;137(9):2814–2822. [PubMed] [Google Scholar]
- Depper J. M., Leonard W. J., Krönke M., Noguchi P. D., Cunningham R. E., Waldmann T. A., Greene W. C. Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen. J Immunol. 1984 Dec;133(6):3054–3061. [PubMed] [Google Scholar]
- Dukovich M., Wano Y., Le thi Bich Thuy, Katz P., Cullen B. R., Kehrl J. H., Greene W. C. A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature. 1987 Jun 11;327(6122):518–522. doi: 10.1038/327518a0. [DOI] [PubMed] [Google Scholar]
- Gray J. D., Shau H. Y., Golub S. H. Functional studies on the precursors of human lymphokine-activated killer cells. Cell Immunol. 1985 Dec;96(2):338–350. doi: 10.1016/0008-8749(85)90365-x. [DOI] [PubMed] [Google Scholar]
- Griffin J. D., Hercend T., Beveridge R., Schlossman S. F. Characterization of an antigen expressed by human natural killer cells. J Immunol. 1983 Jun;130(6):2947–2951. [PubMed] [Google Scholar]
- Grimm E. A., Mazumder A., Zhang H. Z., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982 Jun 1;155(6):1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grimm E. A., Ramsey K. M., Mazumder A., Wilson D. J., Djeu J. Y., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med. 1983 Mar 1;157(3):884–897. doi: 10.1084/jem.157.3.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammer S. M., Gillis J. M. Effects of recombinant interleukin-2 on resting human T lymphocytes. J Biol Response Mod. 1986 Feb;5(1):36–44. [PubMed] [Google Scholar]
- Hemler M. E., Brenner M. B., McLean J. M., Strominger J. L. Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2172–2175. doi: 10.1073/pnas.81.7.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itoh K., Tilden A. B., Kumagai K., Balch C. M. Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. J Immunol. 1985 Feb;134(2):802–807. [PubMed] [Google Scholar]
- Kay H. D., Horwitz D. A. Evidence by reactivity with hybridoma antibodies for a probable myeloid origin of peripheral blood cells active in natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity. J Clin Invest. 1980 Oct;66(4):847–851. doi: 10.1172/JCI109923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanier L. L., Kipps T. J., Phillips J. H. Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089–2106. doi: 10.1084/jem.162.6.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
- Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
- Lifson J., Raubitschek A., Benike C., Koths K., Ammann A., Sondel P., Engleman E. Purified interleukin-2 induces proliferation of fresh human lymphocytes in the absence of exogenous stimuli. J Biol Response Mod. 1986 Feb;5(1):61–72. [PubMed] [Google Scholar]
- Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
- Perussia B., Trinchieri G., Jackson A., Warner N. L., Faust J., Rumpold H., Kraft D., Lanier L. L. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed] [Google Scholar]
- Phillips J. H., Lanier L. L. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med. 1986 Sep 1;164(3):814–825. doi: 10.1084/jem.164.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips J. H., Warner N. L., Lanier L. L. Correlation of biophysical properties and cell surface antigenic profile of Percoll gradient-separated human natural killer cells. Nat Immun Cell Growth Regul. 1983;3(2):73–86. [PubMed] [Google Scholar]
- Robb R. J., Rusk C. M., Yodoi J., Greene W. C. Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2002–2006. doi: 10.1073/pnas.84.7.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross G. D., Cain J. A., Lachmann P. J. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed] [Google Scholar]
- Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
- Sharon M., Klausner R. D., Cullen B. R., Chizzonite R., Leonard W. J. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. doi: 10.1126/science.3095922. [DOI] [PubMed] [Google Scholar]
- Smith K. A. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. doi: 10.1146/annurev.iy.02.040184.001535. [DOI] [PubMed] [Google Scholar]
- Smith K. A., Ruscetti F. W. T-cell growth factor and the culture of cloned functional T cells. Adv Immunol. 1981;31:137–175. doi: 10.1016/s0065-2776(08)60920-7. [DOI] [PubMed] [Google Scholar]
- Talmadge J. E., Wiltrout R. H., Counts D. F., Herberman R. B., McDonald T., Ortaldo J. R. Proliferation of human peripheral blood lymphocytes induced by recombinant human interleukin 2: contribution of large granular lymphocytes and T lymphocytes. Cell Immunol. 1986 Oct 15;102(2):261–272. doi: 10.1016/0008-8749(86)90420-x. [DOI] [PubMed] [Google Scholar]
- Taylor D. S., Kern J. A., Nowell P. C. IL 2 alone is mitogenic only for Tac-positive lymphocytes in human peripheral blood. J Immunol. 1986 Mar 1;136(5):1620–1624. [PubMed] [Google Scholar]
- Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trinchieri G., Matsumoto-Kobayashi M., Clark S. C., Seehra J., London L., Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. doi: 10.1084/jem.160.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. doi: 10.1073/pnas.83.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zarling J. M., Clouse K. A., Biddison W. E., Kung P. C. Phenotypes of human natural killer cell populations detected with monoclonal antibodies. J Immunol. 1981 Dec;127(6):2575–2580. [PubMed] [Google Scholar]
- Zarling J. M., Kung P. C. Monoclonal antibodies which distinguish between human NK cells and cytotoxic T lymphocytes. Nature. 1980 Nov 27;288(5789):394–396. doi: 10.1038/288394a0. [DOI] [PubMed] [Google Scholar]
