• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. May 1991; 87(5): 1773–1779.
PMCID: PMC295289

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hogg N. The structure and function of Fc receptors. Immunol Today. 1988 Jul-Aug;9(7-8):185–187. [PubMed]
  • Fanger MW, Shen L, Graziano RF, Guyre PM. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. [PubMed]
  • Anderson CL, Guyre PM, Whitin JC, Ryan DH, Looney RJ, Fanger MW. 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]
  • Fleit HB, Wright SD, Unkeless JC. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. [PMC free article] [PubMed]
  • Unkeless JC. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest. 1989 Feb;83(2):355–361. [PMC free article] [PubMed]
  • Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989 Nov 15;74(7):2527–2534. [PubMed]
  • Clarkson SB, Ory PA. CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes. J Exp Med. 1988 Feb 1;167(2):408–420. [PMC free article] [PubMed]
  • Welch GR, Wong HL, Wahl SM. Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta. J Immunol. 1990 May 1;144(9):3444–3448. [PubMed]
  • Homsy J, Meyer M, Tateno M, Clarkson S, Levy JA. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. [PubMed]
  • Robinson WE, Jr, Montefiori DC, Mitchell WM. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. [PubMed]
  • Robinson WE, Jr, Montefiori DC, Mitchell WM. 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. [PubMed]
  • Bolognesi DP. Progress in vaccines against AIDS. Science. 1989 Dec 8;246(4935):1233–1234. [PubMed]
  • Smith PD, Ohura K, Masur H, Lane HC, Fauci AS, Wahl SM. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis. J Clin Invest. 1984 Dec;74(6):2121–2128. [PMC free article] [PubMed]
  • Allen JB, McCartney-Francis N, Smith PD, Simon G, Gartner S, Wahl LM, Popovic M, Wahl SM. 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. [PMC free article] [PubMed]
  • Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, Arthur LO, Farrar WL, Wahl LM. 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]
  • Berman MA, Sandborg CI, Calabia BS, Andrews BS, Friou GJ. Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). Clin Immunol Immunopathol. 1987 Jan;42(1):133–140. [PubMed]
  • Roux-Lombard P, Aladjem D, Balavoine JF, Chofflon M, Despont JP, Hirschel B, Jeannet M, Kapanci Y, Lang R, Toccanier MF, et al. 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. [PubMed]
  • Roy S, Wainberg MA. Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). J Leukoc Biol. 1988 Jan;43(1):91–97. [PubMed]
  • Edelman AS, Zolla-Pazner S. AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency. FASEB J. 1989 Jan;3(1):22–30. [PubMed]
  • Wahl LM, Katona IM, Wilder RL, Winter CC, Haraoui B, Scher I, Wahl SM. 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Reed JC, Alpers JD, Nowell PC. 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. [PMC free article] [PubMed]
  • Wahl SM, Hunt DA, Wong HL, Dougherty S, McCartney-Francis N, Wahl LM, Ellingsworth L, Schmidt JA, Hall G, Roberts AB, et al. 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]
  • Perussia B, Trinchieri G, Jackson A, Warner NL, Faust J, Rumpold H, Kraft D, Lanier LL. 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]
  • O'Connor-McCourt MD, Wakefield LM. 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]
  • Pinching AJ, McManus TJ, Jeffries DJ, Moshtael O, Donaghy M, Parkin JM, Munday PE, Harris JR. Studies of cellular immunity in male homosexuals in London. Lancet. 1983 Jul 16;2(8342):126–130. [PubMed]
  • Bender BS, Frank MM, Lawley TJ, Smith WJ, Brickman CM, Quinn TC. Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Aug;152(2):409–412. [PubMed]
  • Bender BS, Auger FA, Quinn TC, Redfield R, Gold J, Folks TM. 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]
  • Bender BS, Davidson BL, Kline R, Brown C, Quinn TC. 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. [PubMed]
  • Davidson BL, Kline RL, Rowland J, Quinn TC. Surface markers of monocyte function and activation in AIDS. J Infect Dis. 1988 Aug;158(2):483–486. [PubMed]
  • Fries LF, Brickman CM, Frank MM. 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]
  • Hosea SW, Brown EJ, Hamburger MI, Frank MM. Opsonic requirements for intravascular clearance after splenectomy. N Engl J Med. 1981 Jan 29;304(5):245–250. [PubMed]
  • Katayama S, Chia D, Nasu H, Knutson DW. 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]
  • Salky NK, Mills D, Di Luzio NR. Activity of the reticuloendothelial system in diseases of altered immunity. J Lab Clin Med. 1965 Dec;66(6):952–960. [PubMed]
  • Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. [PubMed]
  • Guyre PM, Crabtree GR, Bodwell JE, Munck A. MLC-conditioned media stimulate an increase in Fc receptors on human macrophages. J Immunol. 1981 Feb;126(2):666–668. [PubMed]
  • Guyre PM, Morganelli PM, Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. [PMC free article] [PubMed]
  • Liesveld JL, Abboud CN, Looney RJ, Ryan DH, Brennan JK. 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]
  • Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-beta. Immunol Today. 1989 Aug;10(8):258–261. [PubMed]
  • Wahl SM, Hunt DA, Bansal G, McCartney-Francis N, Ellingsworth L, Allen JB. Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta. J Exp Med. 1988 Oct 1;168(4):1403–1417. [PMC free article] [PubMed]
  • Fontana A, Frei K, Bodmer S, Hofer E, Schreier MH, Palladino MA, Jr, Zinkernagel RM. 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]
  • Kehrl JH, Roberts AB, Wakefield LM, Jakowlew S, Sporn MB, Fauci AS. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986 Dec 15;137(12):3855–3860. [PubMed]
  • Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. 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. [PMC free article] [PubMed]
  • Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. 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. [PMC free article] [PubMed]
  • Wahl SM, McCartney-Francis N, Allen JB, Dougherty EB, Dougherty SF. Macrophage production of TGF-beta and regulation by TGF-beta. Ann N Y Acad Sci. 1990;593:188–196. [PubMed]
  • 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. [PubMed]
  • Wahl SM, Allen JB, McCartney-Francis N, Morganti-Kossmann MC, Kossmann T, Ellingsworth L, Mai UE, Mergenhagen SE, Orenstein JM. 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. [PMC free article] [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...