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J Clin Invest. 1988 December; 82(6): 1908–1914.
PMCID: PMC442771

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

Abstract

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.

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Selected References

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  • Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. [PubMed]
  • Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai B, et al. 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. [PubMed]
  • Levy JA, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oshiro LS. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. [PubMed]
  • Klatzmann D, Barré-Sinoussi F, Nugeyre MT, Danquet C, Vilmer E, Griscelli C, Brun-Veziret F, Rouzioux C, Gluckman JC, Chermann JC, et al. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. [PubMed]
  • Ho DD, Rota TR, Hirsch MS. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. [PMC free article] [PubMed]
  • Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. [PubMed]
  • Armstrong JA, Horne R. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet. 1984 Aug 18;2(8399):370–372. [PubMed]
  • Montagnier L, Gruest J, Chamaret S, Dauguet C, Axler C, Guétard D, Nugeyre MT, Barré-Sinoussi F, Chermann JC, Brunet JB, et al. Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines. Science. 1984 Jul 6;225(4657):63–66. [PubMed]
  • Tersmette M, Miedema F, Huisman HG, Goudsmit J, Melief CJ. Productive HTLV-III infection of human B cell lines. Lancet. 1985 Apr 6;1(8432):815–816. [PubMed]
  • Bowen DL, Lane HC, Fauci AS. Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):704–709. [PubMed]
  • Lane HC, Depper JM, Greene WC, Whalen G, Waldmann TA, Fauci AS. 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. [PubMed]
  • Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. [PubMed]
  • Ammann AJ, Schiffman G, Abrams D, Volberding P, Ziegler J, Conant M. B-cell immunodeficiency in acquired immune deficiency syndrome. JAMA. 1984 Mar 16;251(11):1447–1449. [PubMed]
  • Rook AH, Masur H, Lane HC, Frederick W, Kasahara T, Macher AM, Djeu JY, Manischewitz JF, Jackson L, Fauci AS, et al. Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. J Clin Invest. 1983 Jul;72(1):398–403. [PMC free article] [PubMed]
  • Yarchoan R, Redfield RR, Broder S. Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus. J Clin Invest. 1986 Aug;78(2):439–447. [PMC free article] [PubMed]
  • Schnittman SM, Lane HC, Higgins SE, Folks T, Fauci AS. Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. Science. 1986 Sep 5;233(4768):1084–1086. [PubMed]
  • Miedema F, Van Oostveen JW, Sauerwein RW, Terpstra FG, Aarden LA, Melief CJ. Induction of immunoglobulin synthesis by interleukin 2 is T4+/T8- cell dependent. A role for interleukin 2 in the pokeweed mitogen-driven system. Eur J Immunol. 1985 Feb;15(2):107–112. [PubMed]
  • van Lier RA, Borst J, Vroom TM, Klein H, Van Mourik P, Zeijlemaker WP, Melief CJ. Tissue distribution and biochemical and functional properties of Tp55 (CD27), a novel T cell differentiation antigen. J Immunol. 1987 Sep 1;139(5):1589–1596. [PubMed]
  • Miedema F, van Oostveen JW, Terpstra FG, van den Wall Bake AW, Willemze R, Rauws EA, Bieger R, van 't Veer MB, Catovsky D, Melief CJ. Analysis of helper activity on pokeweed mitogen- and interleukin 2-driven immunoglobulin synthesis by neoplastic T4+ cells. J Clin Invest. 1985 Dec;76(6):2139–2143. [PMC free article] [PubMed]
  • Rümke HC, Terpstra FG, Huis B, Out TA, Zeijlemaker WP. Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors. J Immunol. 1982 Feb;128(2):696–701. [PubMed]
  • Tax WJ, Willems HW, Reekers PP, Capel PJ, Koene RA. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature. 1983 Aug 4;304(5925):445–447. [PubMed]
  • Nakagawa N, Nakagawa T, Volkman DJ, Ambrus JL, Jr, Fauci AS. The role of interleukin 2 in inducing Ig production in a pokeweed mitogen-stimulated mononuclear cell system. J Immunol. 1987 Feb 1;138(3):795–801. [PubMed]
  • Kuritani T, Cooper MD. Human B cell differentiation. II. Pokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation. J Exp Med. 1982 May 1;155(5):1561–1566. [PMC free article] [PubMed]
  • Jelinek DF, Splawski JB, Lipsky PE. Human peripheral blood B lymphocyte subpopulations: functional and phenotypic analysis of surface IgD positive and negative subsets. J Immunol. 1986 Jan;136(1):83–92. [PubMed]
  • Tung KS, Koster F, Bernstein DC, Kriebel PW, Payne SM, Shearer GM. Elevated allogeneic cytotoxic T lymphocyte activity in peripheral blood leukocytes of homosexual men. J Immunol. 1985 Nov;135(5):3163–3171. [PubMed]
  • Nicholson JK, McDougal JS, Spira TJ, Cross GD, Jones BM, Reinherz EL. Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy. J Clin Invest. 1984 Jan;73(1):191–201. [PMC free article] [PubMed]
  • Martínez-Maza O, Crabb E, Mitsuyasu RT, Fahey JL, Giorgi JV. Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity. J Immunol. 1987 Jun 1;138(11):3720–3724. [PubMed]
  • Sedgwick JD, Holt PG. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. [PubMed]
  • Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. [PMC free article] [PubMed]
  • Prince HE, Moody DJ, Shubin BI, Fahey JL. 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. [PubMed]
  • Salahuddin SZ, Rose RM, Groopman JE, Markham PD, Gallo RC. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed]
  • Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. [PubMed]
  • Gartner S, Markovits P, Markovitz DM, Betts RF, 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]
  • Petit AJ, Tersmette M, Terpstra FG, de Goede RE, van Lier RA, Miedema F. Decreased accessory cell function by human monocytic cells after infection with HIV. J Immunol. 1988 Mar 1;140(5):1485–1489. [PubMed]
  • Harper ME, Marselle LM, Gallo RC, Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. [PubMed]
  • Metz SA. Glucose increases the synthesis of lipoxygenase-mediated metabolites of arachidonic acid in intact rat islets. Proc Natl Acad Sci U S A. 1985 Jan;82(1):198–202. [PubMed]
  • Shalaby MR, Krowka JF, Gregory TJ, Hirabayashi SE, McCabe SM, Kaufman DS, Stites DP, Ammann AJ. The effects of human immunodeficiency virus recombinant envelope glycoprotein on immune cell functions in vitro. Cell Immunol. 1987 Nov;110(1):140–148. [PubMed]
  • Mann DL, Lasane F, Popovic M, Arthur LO, Robey WG, Blattner WA, Newman MJ. HTLV-III large envelope protein (gp120) suppresses PHA-induced lymphocyte blastogenesis. J Immunol. 1987 Apr 15;138(8):2640–2644. [PubMed]
  • Fauci AS. Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res. 1984 Dec;32(5):491–499. [PubMed]
  • Donahue RE, Johnson MM, Zon LI, Clark SC, Groopman JE. Suppression of in vitro haematopoiesis following human immunodeficiency virus infection. Nature. 1987 Mar 12;326(6109):200–203. [PubMed]
  • Carne CA, Weller IV, Waite J, Briggs M, Pearce F, Adler MW, Tedder RS. Impaired responsiveness of homosexual men with HIV antibodies to plasma derived hepatitis B vaccine. Br Med J (Clin Res Ed) 1987 Apr 4;294(6576):866–868. [PMC free article] [PubMed]
  • Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med. 1987 Mar 12;316(11):673–676. [PubMed]

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