Abstract
We investigated the relationship of soluble interleukin 2 receptor (sIL2R) production to cellular IL2R expression and DNA synthesis by mitogen-stimulated mononuclear cells from blood donors seropositive for human immunodeficiency virus (HIV). SIL2R was measured using an enzyme-linked immunosorbent assay which employed 2 anti-IL2R monoclonal antibodies recognizing distinct IL2R epitopes. Decreased phytohemagglutinin-induced DNA synthesis and cellular IL2R expression were accompanied by decreased levels of sIL2R in cell culture supernatants. Similar findings were observed for pokeweed mitogen-induced responses. There was no detectable spontaneous secretion of sIL2R into culture supernatants by unstimulated mononuclear cells from either HIV-seropositive or control seronegative donors. These findings indicate that thein vitro T-cell activation defects which characterize HIV infection include decreased sIL2R production, as well as decreased cellular IL2R expression and DNA synthesis. Further, they show that assessment of supernatant sIL2R levels can be used as a valid, reliable assay for T-cell activation.
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References
Robb RJ: Interleukin 2: The molecule and its function. Immunol Today 5:203–209, 1984
Robb RJ, Greene WC, Rusk CM: Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med 160:1126–1146, 1984
Uchiyama T, Broder S, Waldmann T: A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol 126:1393–1397, 1981
Williams JM, Abbud-Filho M, Kelley VE, Strom TB: Interleukin 2 apparently upregulates its receptor and induces proliferation of various mononuclear leukocytes in the absence of antigen. Cell Immunol 94:383–393, 1985
Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135:3172–3177, 1985
Nelson DL, Rubin LA, Kurman CC, Fritz ME, Boutin B: An analysis of the cellular requirements for the production of soluble interleukin 2 receptors in vitro. J Clin Immunol 6:114–120, 1986
Teshigawara K, Wang H-M, Kato K, Smith KA: Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med 165:223–238, 1987
Robb RJ, Greene WC: Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor. J Exp Med 165:1201–1206, 1987
Rubin LA, Jay G, Nelson DL: The released interleukin 2 receptor binds interleukin 2 efficiently. J Immunol 137:3841–3844, 1986
Robb RJ, Kutny RM: Structure-function relationships for the IL2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein. J Immunol 139:855–862, 1987
Prince HE, Kermani-Arab V, Fahey JL: Depressed interleukin 2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes. J Immunol 133:1313–1317, 1984
Munn CG, Reuben JM, Hersh EM, Mansell PWA, Newell GR: T cell surface antigen expression on lymphocytes of patients with AIDS during in vitro mitogen stimulation. Cancer Immunol Immunother 18:141–148, 1984
Ebert EC, Stoll DB, Casseus BJ, Lipshutz WH, Hauptman SP: Diminished interleukin 2 production and receptor generation characterize the acquired immunodeficiency syndrome. Clin Immunol Immunopathol 37:282–297, 1985
Gupta S: Study of activated T cells in man. II. Interleukin 2 receptor and transferrin receptor expression on T cells and production of interleukin 2 in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Clin Immunol Immunopathol 38:93–100, 1986
Sethi KK, Naher H: Elevated titers of cell-free interleukin 2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome. Immunol Lett 13:179–184, 1986
Miller JP, Kloster B, Rubin L, Shearer G, Nelson D, Tomar R: Soluble IL2 receptors (sIL2R) in HTLV-III/LAV infected populations. Abstr Int Congr AIDS 3.54.33, 1986
Kleinman S, Anton-Guirgis H, Culver BD, Taylor TH, Prince HE, Kaplan HS: Anti-HTLV III ELISA and western blot testing in a blood donor population: Implications for donor notification. Vox Sang 51:143–147, 1986
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 (Suppl 97):334–339, 1968
Prince HE, John JK: Unique pattern of interleukin 2 receptor expression by lymphocytes in response to anti-Leu 4 monoclonal antibody: Relationship to monocyte accessory cell function. Diag Immunol 4:241–246, 1986
Reinherz EL, Schlossman SF: The differentiation and function of human T lymphocytes. Cell 19:821–827, 1980
Fahey JL, Prince H, Weaver M, Groopman J, Visscher B, Schwartz K, Detels R: Quantitative changes in T helper or T suppressor/cytotoxic lymphocytes subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Am J Med 76:95–100, 1984
Prince HE, John JK: Early activation marker expression to detect impaired proliferative responses to pokeweed mitogen and tetanus toxoid: Studies in patients with AIDS and related disorders. Diag Immunol 4:306–311, 1986
Radvany RM, Schubert MS, Kiamar M, Jarzabek V, Koehler-Carone K, Kuban D, Hecht F: Lymphocyte subpopulation profiles and mitogen kinetics in immunological deficiency testing. J Clin Immunol 7:312–318, 1987
Prince HE, John JK: Abnormalities of interleukin 2 receptor expression associated with decreased antigen-induced lymphocyte proliferation in patients with AIDS and related disorders. Clin Exp Immunol 67:59–65, 1987
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Prince, H.E., Kleinman, S.H., Maino, V.C. et al. In vitro activation of T lymphocytes from human immunodeficiency virus (HIV)-seropositive blood donors. I. Soluble interleukin 2 receptor (IL2R) production parallels cellular IL2R expression and DNA synthesis. J Clin Immunol 8, 114–120 (1988). https://doi.org/10.1007/BF00917899
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DOI: https://doi.org/10.1007/BF00917899