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. 1990 Jan;85(1):192–199. doi: 10.1172/JCI114412

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 B Allen 1, N McCartney-Francis 1, P D Smith 1, G Simon 1, S Gartner 1, L M Wahl 1, M Popovic 1, S M Wahl 1
PMCID: PMC296405  PMID: 2295695

Abstract

A population of circulating mononuclear cells from patients with AIDS was identified which expressed interleukin 2 receptors (IL-2R). By dual-fluorescence flow microfluorometry, the patients' IL-2R+ cells were further identified as Leu M3+ monocytes (29.4 +/- 5.2% of the Leu M3+ cells were IL-2R+, n = 15), whereas Leu M3+ monocytes from normal subjects were IL-2R negative (2.0 +/- 0.42%; P less than 0.001). By Northern analysis, monocytes from AIDS patients, but not control subjects, constitutively expressed steady-state levels of IL-2R mRNA. Functionally, the IL-2R+ monocytes were capable of depleting IL-2 from culture supernatants, suggesting a mechanism for the reduced IL-2 levels commonly seen in AIDS patients. IL-2R+ monocytes also expressed increased levels of surface HLA-DR which may favor monocyte T-cell interactions and the transmission of human immunodeficiency virus (HIV). In additional studies, normal monocytes were infected with a macrophage-tropic HIV isolate in vitro and monitored for IL-2R and HLA-DR expression. Within 24-48 h after exposure to HIV in vitro, but before evidence of productive infection, greater than 25% of the monocytes became IL-2R+ with increasing numbers of IL-2R+ cells and HLA-DR levels through day 6. These early signaling effects of HIV could be mimicked by adding purified HIV envelope glycoprotein gp120 to the monocytes. This stimulation of monocytes before or independent of productive infection of the cells by HIV is consistent with in vivo observations of activated and/or abnormal functions by monocytes that do not appear to be infected with HIV in AIDS patients.

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Selected References

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  1. Ascher M. S., Sheppard H. W. AIDS as immune system activation: a model for pathogenesis. Clin Exp Immunol. 1988 Aug;73(2):165–167. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  4. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Epstein L. G., Sharer L. R., Cho E. S., Myenhofer M., Navia B., Price R. W. HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res. 1984;1(6):447–454. doi: 10.1089/aid.1.1983.1.447. [DOI] [PubMed] [Google Scholar]
  7. Estevez M. E., Ballart I. J., Diez R. A., Planes N., Scaglione C., Sen L. Early defect of phagocytic cell function in subjects at risk for acquired immunodeficiency syndrome. Scand J Immunol. 1986 Aug;24(2):215–221. doi: 10.1111/j.1365-3083.1986.tb02088.x. [DOI] [PubMed] [Google Scholar]
  8. Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res. 1984 Dec;32(5):491–499. [PubMed] [Google Scholar]
  9. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  10. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  11. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heagy W., Kelley V. E., Strom T. B., Mayer K., Shapiro H. M., Mandel R., Finberg R. Decreased expression of human class II antigens on monocytes from patients with acquired immune deficiency syndrome. Increased expression with interferon-gamma. J Clin Invest. 1984 Dec;74(6):2089–2096. doi: 10.1172/JCI111633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Herrmann F., Cannistra S. A., Levine H., Griffin J. D. Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells. J Exp Med. 1985 Sep 1;162(3):1111–1116. doi: 10.1084/jem.162.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ho D. D., Rota T. R., Hirsch M. S. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. doi: 10.1172/JCI112491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holter W., Goldman C. K., Casabo L., Nelson D. L., Greene W. C., Waldmann T. A. Expression of functional IL 2 receptors by lipopolysaccharide and interferon-gamma stimulated human monocytes. J Immunol. 1987 May 1;138(9):2917–2922. [PubMed] [Google Scholar]
  16. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  17. Kloster B. E., John P. A., Miller L. E., Rubin L. A., Nelson D. L., Blair D. C., Tomar R. H. Soluble interleukin 2 receptors are elevated in patients with AIDS or at risk of developing AIDS. Clin Immunol Immunopathol. 1987 Dec;45(3):440–446. doi: 10.1016/0090-1229(87)90095-x. [DOI] [PubMed] [Google Scholar]
  18. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  19. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  20. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  21. Levy J. A., Shimabukuro J., McHugh T., Casavant C., Stites D., Oshiro L. AIDS-associated retroviruses (ARV) can productively infect other cells besides human T helper cells. Virology. 1985 Dec;147(2):441–448. doi: 10.1016/0042-6822(85)90146-1. [DOI] [PubMed] [Google Scholar]
  22. Locksley R. M., Crowe S., Sadick M. D., Heinzel F. P., Gardner K. D., Jr, McGrath M. S., Mills J. Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. J Clin Invest. 1988 Dec;82(6):2097–2105. doi: 10.1172/JCI113831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maggi E., Macchia D., Parronchi P., Mazzetti M., Ravina A., Milo D., Romagnani S. Reduced production of interleukin 2 and interferon-gamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS. Eur J Immunol. 1987 Dec;17(12):1685–1690. doi: 10.1002/eji.1830171202. [DOI] [PubMed] [Google Scholar]
  24. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  25. Nakajima K., Martínez-Maza O., Hirano T., Breen E. C., Nishanian P. G., Salazar-Gonzalez J. F., Fahey J. L., Kishimoto T. Induction of IL-6 (B cell stimulatory factor-2/IFN-beta 2) production by HIV. J Immunol. 1989 Jan 15;142(2):531–536. [PubMed] [Google Scholar]
  26. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  27. Pauza C. D. HIV persistence in monocytes leads to pathogenesis and AIDS. Cell Immunol. 1988 Apr 1;112(2):414–424. doi: 10.1016/0008-8749(88)90310-3. [DOI] [PubMed] [Google Scholar]
  28. Perno C. F., Yarchoan R., Cooney D. A., Hartman N. R., Gartner S., Popovic M., Hao Z., Gerrard T. L., Wilson Y. A., Johns D. G. Inhibition of human immunodeficiency virus (HIV-1/HTLV-IIIBa-L) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2',3'-dideoxynucleosides. J Exp Med. 1988 Sep 1;168(3):1111–1125. doi: 10.1084/jem.168.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Poli G., Bottazzi B., Acero R., Bersani L., Rossi V., Introna M., Lazzarin A., Galli M., Mantovani A. Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis. Clin Exp Immunol. 1985 Oct;62(1):136–142. [PMC free article] [PubMed] [Google Scholar]
  30. Prince H. E., Kermani-Arab V., Fahey J. L. Depressed interleukin 2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes. J Immunol. 1984 Sep;133(3):1313–1317. [PubMed] [Google Scholar]
  31. Prince H. E., Kleinman S., Williams A. E. Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV. J Immunol. 1988 Feb 15;140(4):1139–1141. [PubMed] [Google Scholar]
  32. Prince H. E., Moody D. J., Shubin B. I., Fahey J. L. Defective monocyte function in acquired immune deficiency syndrome (AIDS): evidence from a monocyte-dependent T-cell proliferative system. J Clin Immunol. 1985 Jan;5(1):21–25. doi: 10.1007/BF00915164. [DOI] [PubMed] [Google Scholar]
  33. Pyle S. W., Dubois G. C., Robey W. G., Bess J. W., Jr, Fischinger P. J., Arthur L. O. Purification and characterization of the external envelope glycoprotein from two human immunodeficiency virus type 1 variants, HTLV-IIIB and HTLV-IIIRF. J Virol. 1988 Jul;62(7):2258–2264. doi: 10.1128/jvi.62.7.2258-2264.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reddy M. M., Grieco M. H. Elevated soluble interleukin-2 receptor levels in serum of human immunodeficiency virus infected populations. AIDS Res Hum Retroviruses. 1988 Apr;4(2):115–120. doi: 10.1089/aid.1988.4.115. [DOI] [PubMed] [Google Scholar]
  35. Robb R. J., Kutny R. M. Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein. J Immunol. 1987 Aug 1;139(3):855–862. [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Salahuddin S. Z., Rose R. M., Groopman J. E., Markham P. D., Gallo R. C. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed] [Google Scholar]
  39. Sei Y., Petrella R. J., Tsang P., Bekesi J. G., Yokoyama M. M. Monocytes in AIDS. N Engl J Med. 1986 Dec 18;315(25):1611–1612. doi: 10.1056/NEJM198612183152512. [DOI] [PubMed] [Google Scholar]
  40. Sethi K. K., Näher H. Elevated titers of cell-free interleukin-2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome. Immunol Lett. 1986 Oct;13(4):179–184. doi: 10.1016/0165-2478(86)90052-0. [DOI] [PubMed] [Google Scholar]
  41. Shannon K., Cowan M. J., Ball E., Abrams D., Volberding P., Ammann A. J. Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells. J Clin Immunol. 1985 Jul;5(4):239–245. doi: 10.1007/BF00929458. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Szebeni J., Wahl S. M., Popovic M., Wahl L. M., Gartner S., Fine R. L., Skaleric U., Friedmann R. M., Weinstein J. N. Dipyridamole potentiates the inhibition by 3'-azido-3'-deoxythymidine and other dideoxynucleosides of human immunodeficiency virus replication in monocyte-macrophages. Proc Natl Acad Sci U S A. 1989 May;86(10):3842–3846. doi: 10.1073/pnas.86.10.3842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tsang K. Y., Fudenberg H. H., Galbraith G. M., Donnelly R. P., Bishop L. R., Koopmann W. R. Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. J Clin Invest. 1985 May;75(5):1538–1544. doi: 10.1172/JCI111858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tschachler E., Groh V., Popovic M., Mann D. L., Konrad K., Safai B., Eron L., diMarzo Veronese F., Wolff K., Stingl G. Epidermal Langerhans cells--a target for HTLV-III/LAV infection. J Invest Dermatol. 1987 Feb;88(2):233–237. doi: 10.1111/1523-1747.ep12525402. [DOI] [PubMed] [Google Scholar]
  46. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. 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]
  49. 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]
  50. Wahl S. M., McCartney-Francis N., Hunt D. A., Smith P. D., Wahl L. M., Katona I. M. Monocyte interleukin 2 receptor gene expression and interleukin 2 augmentation of microbicidal activity. J Immunol. 1987 Aug 15;139(4):1342–1347. [PubMed] [Google Scholar]
  51. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. doi: 10.1073/pnas.83.18.7089. [DOI] [PMC free article] [PubMed] [Google Scholar]

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