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. 1987 Jun;79(6):1883–1889. doi: 10.1172/JCI113032

Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells.

A J Petit, F G Terpstra, F Miedema
PMCID: PMC424534  PMID: 3108323

Abstract

We studied the effect of human immunodeficiency virus (HIV) infection on the surface-marker expression of the human promonocytic cell line U937. U937 cells persistently produced HIV as detected by reverse transcriptase activity in culture supernatant. Expression of HLA class II antigens on U937/HIV cells was decreased 2- to 10-fold, depending on the Mab used. Class II expression of U937/HIV cells increased approximately two-fold by treatment with r-interferon-gamma. Whereas noninfected U937 cells expressed moderate amounts of lymphocyte function-associated antigen-1 (LFA-1) (CD11a) and minimal amounts of the C3bi receptor (CD11b) and p150/95 (CD11c), U937/HIV cells expressed moderate amounts of C3bi receptor and p150/95 and showed elevated expression of LFA-1 alpha (CD11a) and -beta (CD18) chains. Expression of these adhesion molecules resulted in strongly enhanced phorbolester-induced aggregation of U937/HIV cells compared with the noninfected U937 cells. In addition, almost all U937/HIV cells, but not noninfected U937 cells, intensely stained for cytoplasmic nonspecific esterase activity. The effects of HIV infection on U937 cells strikingly resemble the effects of differentiation-inducing agents, such as PMA and DMSO, on the U937 phenotype. Our finding suggests that HIV infection, apart from down regulating class II expression, induces differentiation of U937 cells.

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Selected References

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  1. Belsito D. V., Sanchez M. R., Baer R. L., Valentine F., Thorbecke G. J. Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1984 May 17;310(20):1279–1282. doi: 10.1056/NEJM198405173102002. [DOI] [PubMed] [Google Scholar]
  2. Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
  3. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  4. Brodsky F. M., Parham P. Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants. J Immunol. 1982 Jan;128(1):129–135. [PubMed] [Google Scholar]
  5. Capobianchi M. R., Ameglio F., Tosi R., Dolei A. Differences in the expression and release of DR, BR, and DQ molecules in human cells treated with recombinant interferon gamma: comparison to other interferons. Hum Immunol. 1985 May;13(1):1–11. doi: 10.1016/0198-8859(85)90022-9. [DOI] [PubMed] [Google Scholar]
  6. Dayton A. I., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986 Mar 28;44(6):941–947. doi: 10.1016/0092-8674(86)90017-6. [DOI] [PubMed] [Google Scholar]
  7. Fleit H. B., Wright S. D., Durie C. J., Valinsky J. E., Unkeless J. C. Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. J Clin Invest. 1984 Feb;73(2):516–525. doi: 10.1172/JCI111238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gendelman H. E., Narayan O., Molineaux S., Clements J. E., Ghotbi Z. Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7086–7090. doi: 10.1073/pnas.82.20.7086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Keizer G. D., Borst J., Figdor C. G., Spits H., Miedema F., Terhorst C., De Vries J. E. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985 Nov;15(11):1142–1148. doi: 10.1002/eji.1830151114. [DOI] [PubMed] [Google Scholar]
  15. Koeffler H. P., Ranyard J., Yelton L., Billing R., Bohman R. Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4080–4084. doi: 10.1073/pnas.81.13.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lane H. C., Depper J. M., Greene W. C., Whalen G., Waldmann T. A., Fauci A. S. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985 Jul 11;313(2):79–84. doi: 10.1056/NEJM198507113130204. [DOI] [PubMed] [Google Scholar]
  17. Lanier L. L., Arnaout M. A., Schwarting R., Warner N. L., Ross G. D. p150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody. Eur J Immunol. 1985 Jul;15(7):713–718. doi: 10.1002/eji.1830150714. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Banapour B., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature. 1986 Oct 23;323(6090):725–728. doi: 10.1038/323725a0. [DOI] [PubMed] [Google Scholar]
  20. Majdic O., Bettelheim P., Stockinger H., Aberer W., Liszka K., Lutz D., Knapp W. M2, a novel myelomonocytic cell surface antigen and its distribution on leukemic cells. Int J Cancer. 1984 May 15;33(5):617–623. doi: 10.1002/ijc.2910330511. [DOI] [PubMed] [Google Scholar]
  21. Matis L. A., Jones P. P., Murphy D. B., Hedrick S. M., Lerner E. A., Janeway C. A., Jr, McNicholas J. M., Schwartz R. H. Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:E alpha complex expression causes a corresponding defect in antigen-presenting cell function. J Exp Med. 1982 Feb 1;155(2):508–523. doi: 10.1084/jem.155.2.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Miedema F., Tetteroo P. A., Hesselink W. G., Werner G., Spits H., Melief C. J. Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity). Eur J Immunol. 1984 Jun;14(6):518–523. doi: 10.1002/eji.1830140607. [DOI] [PubMed] [Google Scholar]
  23. Minta J. O., Pambrun L. In vitro induction of cytologic and functional differentiation of the immature human monocytelike cell line U-937 with phorbol myristate acetate. Am J Pathol. 1985 Apr;119(1):111–126. [PMC free article] [PubMed] [Google Scholar]
  24. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature. 1986 Feb 13;319(6054):555–559. doi: 10.1038/319555a0. [DOI] [PubMed] [Google Scholar]
  27. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  28. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  32. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  33. Springer T. A., Anderson D. C. The importance of the Mac-1, LFA-1 glycoprotein family in monocyte and granulocyte adherence, chemotaxis, and migration into inflammatory sites: insights from an experiment of nature. Ciba Found Symp. 1986;118:102–126. doi: 10.1002/9780470720998.ch8. [DOI] [PubMed] [Google Scholar]
  34. Tersmette M., de Goede R. E., Over J., de Jonge E., Radema H., Lucas C. J., Huisman H. G., Miedema F. Thermal inactivation of human immunodeficiency virus in lyophilised blood products evaluated by ID50 titrations. Vox Sang. 1986;51(3):239–243. doi: 10.1111/j.1423-0410.1986.tb01962.x. [DOI] [PubMed] [Google Scholar]
  35. Tetteroo P. A., Mulder A., Lansdorp P. M., Zola H., Baker D. A., Visser F. J., von dem Borne A. E. Myeloid-associated antigen 3-alpha-fucosyl-N-acetyllactosamine (FAL): location on various granulocyte membrane glycoproteins and masking upon monocytic differentiation. Eur J Immunol. 1984 Dec;14(12):1089–1095. doi: 10.1002/eji.1830141205. [DOI] [PubMed] [Google Scholar]
  36. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]

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