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. 1991 May;87(5):1773–1779. doi: 10.1172/JCI115196

Association of circulating receptor Fc gamma RIII-positive monocytes in AIDS patients with elevated levels of transforming growth factor-beta.

J B Allen 1, H L Wong 1, P M Guyre 1, G L Simon 1, S M Wahl 1
PMCID: PMC295289  PMID: 1708784

Abstract

Monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, Fc gamma RI and Fc gamma RII. In contrast, we have observed that AIDS monocytes express significant levels of a third Fc gamma R, Fc gamma RIII (CD16), which is normally associated with activation or maturation of the monocyte population. By dual-fluorescence analysis using a monoclonal antibody specific for Fc gamma RIII (MAb 3G8), 38.5 +/- 3.2% of the LeuM3 (CD14)-positive monocytes in AIDS patients were CD16 positive as compared to 10.4 +/- 1.0% for healthy individuals (n = 29; P less than 0.005). Furthermore, AIDS monocytes expressed Fc gamma RIII-specific mRNA which is expressed minimally or not at all in control monocytes. As a recently identified inducer of Fc gamma RIII expression on blood monocytes, transforming growth factor-beta (TGF-beta) was found to be elevated in the serum and/or plasma of AIDS patients. Moreover, incubation of normal monocytes with AIDS serum or plasma induced CD16 expression which correlated with serum TGF-beta levels (r = 0.74, P less than 0.001) and was inhibited with a neutralizing antibody to TGF-beta. Thus, the increased CD16 expression on peripheral blood monocytes in AIDS patients may be the consequence of elevated circulating levels of the polypeptide hormone TGF-beta.

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Selected References

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  1. Allen J. B., McCartney-Francis N., Smith P. D., Simon G., Gartner S., Wahl L. M., Popovic M., Wahl S. M. Expression of interleukin 2 receptors by monocytes from patients with acquired immunodeficiency syndrome and induction of monocyte interleukin 2 receptors by human immunodeficiency virus in vitro. J Clin Invest. 1990 Jan;85(1):192–199. doi: 10.1172/JCI114412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson C. L., Guyre P. M., Whitin J. C., Ryan D. H., Looney R. J., Fanger M. W. Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. J Biol Chem. 1986 Sep 25;261(27):12856–12864. [PubMed] [Google Scholar]
  3. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bender B. S., Auger F. A., Quinn T. C., Redfield R., Gold J., Folks T. M. Impaired antibody-dependent cell-mediated cytotoxic activity in patients with the acquired immunodeficiency syndrome. Clin Exp Immunol. 1986 Apr;64(1):166–172. [PMC free article] [PubMed] [Google Scholar]
  5. Bender B. S., Davidson B. L., Kline R., Brown C., Quinn T. C. Role of the mononuclear phagocyte system in the immunopathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Rev Infect Dis. 1988 Nov-Dec;10(6):1142–1154. doi: 10.1093/clinids/10.6.1142. [DOI] [PubMed] [Google Scholar]
  6. Bender B. S., Frank M. M., Lawley T. J., Smith W. J., Brickman C. M., Quinn T. C. Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Aug;152(2):409–412. doi: 10.1093/infdis/152.2.409. [DOI] [PubMed] [Google Scholar]
  7. Berman M. A., Sandborg C. I., Calabia B. S., Andrews B. S., Friou G. J. Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). Clin Immunol Immunopathol. 1987 Jan;42(1):133–140. doi: 10.1016/0090-1229(87)90180-2. [DOI] [PubMed] [Google Scholar]
  8. Bolognesi D. P. Progress in vaccines against AIDS. Science. 1989 Dec 8;246(4935):1233–1234. doi: 10.1126/science.2555922. [DOI] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Clarkson S. B., Ory P. A. CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes. J Exp Med. 1988 Feb 1;167(2):408–420. doi: 10.1084/jem.167.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davidson B. L., Kline R. L., Rowland J., Quinn T. C. Surface markers of monocyte function and activation in AIDS. J Infect Dis. 1988 Aug;158(2):483–486. doi: 10.1093/infdis/158.2.483. [DOI] [PubMed] [Google Scholar]
  12. Edelman A. S., Zolla-Pazner S. AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency. FASEB J. 1989 Jan;3(1):22–30. doi: 10.1096/fasebj.3.1.2562947. [DOI] [PubMed] [Google Scholar]
  13. Fanger M. W., Shen L., Graziano R. F., Guyre P. M. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. doi: 10.1016/0167-5699(89)90234-X. [DOI] [PubMed] [Google Scholar]
  14. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fontana A., Frei K., Bodmer S., Hofer E., Schreier M. H., Palladino M. A., Jr, Zinkernagel R. M. Transforming growth factor-beta inhibits the generation of cytotoxic T cells in virus-infected mice. J Immunol. 1989 Nov 15;143(10):3230–3234. [PubMed] [Google Scholar]
  16. Frank M. M., Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. doi: 10.1056/NEJM197903083001002. [DOI] [PubMed] [Google Scholar]
  17. Fries L. F., Brickman C. M., Frank M. M. Monocyte receptors for the Fc portion of IgG increase in number in autoimmune hemolytic anemia and other hemolytic states and are decreased by glucocorticoid therapy. J Immunol. 1983 Sep;131(3):1240–1245. [PubMed] [Google Scholar]
  18. Guyre P. M., Crabtree G. R., Bodwell J. E., Munck A. MLC-conditioned media stimulate an increase in Fc receptors on human macrophages. J Immunol. 1981 Feb;126(2):666–668. [PubMed] [Google Scholar]
  19. Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hogg N. The structure and function of Fc receptors. Immunol Today. 1988 Jul-Aug;9(7-8):185–187. doi: 10.1016/0167-5699(88)91206-6. [DOI] [PubMed] [Google Scholar]
  21. Homsy J., Meyer M., Tateno M., Clarkson S., Levy J. A. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. doi: 10.1126/science.2786647. [DOI] [PubMed] [Google Scholar]
  22. Hosea S. W., Brown E. J., Hamburger M. I., Frank M. M. Opsonic requirements for intravascular clearance after splenectomy. N Engl J Med. 1981 Jan 29;304(5):245–250. doi: 10.1056/NEJM198101293040501. [DOI] [PubMed] [Google Scholar]
  23. Katayama S., Chia D., Nasu H., Knutson D. W. Increased Fc receptor activity in monocytes from patients with rheumatoid arthritis: a study of monocyte binding and catabolism of soluble aggregates of IgG in vitro. J Immunol. 1981 Aug;127(2):643–647. [PubMed] [Google Scholar]
  24. Kehrl J. H., Roberts A. B., Wakefield L. M., Jakowlew S., Sporn M. B., Fauci A. S. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986 Dec 15;137(12):3855–3860. [PubMed] [Google Scholar]
  25. Kehrl J. H., Wakefield L. M., Roberts A. B., Jakowlew S., Alvarez-Mon M., Derynck R., Sporn M. B., Fauci A. S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. doi: 10.1084/jem.163.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liesveld J. L., Abboud C. N., Looney R. J., Ryan D. H., Brennan J. K. Expression of IgG Fc receptors in myeloid leukemic cell lines. Effect of colony-stimulating factors and cytokines. J Immunol. 1988 Mar 1;140(5):1527–1533. [PubMed] [Google Scholar]
  27. McCartney-Francis N., Mizel D., Wong H., Wahl L., Wahl S. TGF-beta regulates production of growth factors and TGF-beta by human peripheral blood monocytes. Growth Factors. 1990;4(1):27–35. doi: 10.3109/08977199009011007. [DOI] [PubMed] [Google Scholar]
  28. O'Connor-McCourt M. D., Wakefield L. M. Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. J Biol Chem. 1987 Oct 15;262(29):14090–14099. [PubMed] [Google Scholar]
  29. Passlick B., Flieger D., Ziegler-Heitbrock H. W. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989 Nov 15;74(7):2527–2534. [PubMed] [Google Scholar]
  30. 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]
  31. Pinching A. J., McManus T. J., Jeffries D. J., Moshtael O., Donaghy M., Parkin J. M., Munday P. E., Harris J. R. Studies of cellular immunity in male homosexuals in London. Lancet. 1983 Jul 16;2(8342):126–130. doi: 10.1016/s0140-6736(83)90115-0. [DOI] [PubMed] [Google Scholar]
  32. Reed J. C., Alpers J. D., Nowell P. C. Expression of c-myc proto-oncogene in normal human lymphocytes. Regulation by transcriptional and posttranscriptional mechanisms. J Clin Invest. 1987 Jul;80(1):101–106. doi: 10.1172/JCI113034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. A human immunodeficiency virus type 1 (HIV-1) infection-enhancing factor in seropositive sera. Biochem Biophys Res Commun. 1987 Dec 16;149(2):693–699. doi: 10.1016/0006-291x(87)90423-2. [DOI] [PubMed] [Google Scholar]
  34. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  35. Roux-Lombard P., Aladjem D., Balavoine J. F., Chofflon M., Despont J. P., Hirschel B., Jeannet M., Kapanci Y., Lang R., Toccanier M. F. Altered functions of peripheral blood monocytes in homosexual males and intravenous drug users with persistent generalized lymphadenopathy. Eur J Clin Invest. 1986 Jun;16(3):262–270. doi: 10.1111/j.1365-2362.1986.tb01340.x. [DOI] [PubMed] [Google Scholar]
  36. Roy S., Wainberg M. A. Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). J Leukoc Biol. 1988 Jan;43(1):91–97. doi: 10.1002/jlb.43.1.91. [DOI] [PubMed] [Google Scholar]
  37. Salky N. K., Mills D., Di Luzio N. R. Activity of the reticuloendothelial system in diseases of altered immunity. J Lab Clin Med. 1965 Dec;66(6):952–960. [PubMed] [Google Scholar]
  38. Simmons D., Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  39. Smith P. D., Ohura K., Masur H., Lane H. C., Fauci A. S., Wahl S. M. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis. J Clin Invest. 1984 Dec;74(6):2121–2128. doi: 10.1172/JCI111637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Unkeless J. C. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest. 1989 Feb;83(2):355–361. doi: 10.1172/JCI113891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wahl L. M., Katona I. M., Wilder R. L., Winter C. C., Haraoui B., Scher I., Wahl S. M. Isolation of human mononuclear cell subsets by counterflow centrifugal elutriation (CCE). I. Characterization of B-lymphocyte-, T-lymphocyte-, and monocyte-enriched fractions by flow cytometric analysis. Cell Immunol. 1984 May;85(2):373–383. doi: 10.1016/0008-8749(84)90251-x. [DOI] [PubMed] [Google Scholar]
  42. Wahl S. M., Allen J. B., Gartner S., Orenstein J. M., Popovic M., Chenoweth D. E., Arthur L. O., Farrar W. L., Wahl L. M. HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes. J Immunol. 1989 May 15;142(10):3553–3559. [PubMed] [Google Scholar]
  43. Wahl S. M., Allen J. B., McCartney-Francis N., Morganti-Kossmann M. C., Kossmann T., Ellingsworth L., Mai U. E., Mergenhagen S. E., Orenstein J. M. Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med. 1991 Apr 1;173(4):981–991. doi: 10.1084/jem.173.4.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wahl S. M., Hunt D. A., Bansal G., McCartney-Francis N., Ellingsworth L., Allen J. B. Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta. J Exp Med. 1988 Oct 1;168(4):1403–1417. doi: 10.1084/jem.168.4.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wahl S. M., Hunt D. A., Wong H. L., Dougherty S., McCartney-Francis N., Wahl L. M., Ellingsworth L., Schmidt J. A., Hall G., Roberts A. B. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol. 1988 May 1;140(9):3026–3032. [PubMed] [Google Scholar]
  46. Wahl S. M., McCartney-Francis N., Allen J. B., Dougherty E. B., Dougherty S. F. Macrophage production of TGF-beta and regulation by TGF-beta. Ann N Y Acad Sci. 1990;593:188–196. doi: 10.1111/j.1749-6632.1990.tb16111.x. [DOI] [PubMed] [Google Scholar]
  47. Wahl S. M., McCartney-Francis N., Mergenhagen S. E. Inflammatory and immunomodulatory roles of TGF-beta. Immunol Today. 1989 Aug;10(8):258–261. doi: 10.1016/0167-5699(89)90136-9. [DOI] [PubMed] [Google Scholar]
  48. Welch G. R., Wong H. L., Wahl S. M. Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta. J Immunol. 1990 May 1;144(9):3444–3448. [PubMed] [Google Scholar]

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