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Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS)

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Abstract

Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK-associated CD16+ (Leu11) Leu7 and CD16+(Leu11)Leu7+ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8+(Leu2)Leu7+ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8+(Leu2)/Leu7+ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation.

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References

  1. Herberman R: NK Cells and Other Natural Effector Cells. New York, Academic Press, 1982

    Google Scholar 

  2. Lewis DE, Puck JM, Babcock GF, Rich RR: Disproportionate expansion of a minor T cell subset in patients with lymphadenopathy syndrome and acquired immunodeficiency syndrome. J Infect Dis 151:555–559, 1985

    Google Scholar 

  3. Rola-Pleszczynski M, Lieu H: Natural cytotoxic cell activity linked to time of recurrence of herpes labialis. Clin Exp Immunol 55:224–228, 1984

    Google Scholar 

  4. Oldham RK: Natural killer cells: History and significance. J Biol Response Mod 1:217–231, 1982

    Google Scholar 

  5. Lopez C, Kirkpatrick D, Read SE, Fitzgerald PA, Pitt J, Pawha S, Ching CY, Smithwick EM: Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpes virus infections. J Infect Dis 147:1030–1035, 1983

    Google Scholar 

  6. Fauci AS: Immunologic abnormalities in the acquired immune deficiency syndrome (AIDS). Clin Res 32:491–499, 1984

    Google Scholar 

  7. DeShazo RD, Penico JP, Pankey GA, Nordberg JA, Newton JL, Bozelka B, Cortez LM, Daloviso JR: Studies in homosexual patients with and without lymphadenopathy: Relationship to the acquired immune deficiency syndrome. Arch Intern Med 144:1153–1158, 1984

    Google Scholar 

  8. Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai G, White G, Foster P, Markham PD: Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDs and at risk for AIDS. Science 224:500–503, 1983

    Google Scholar 

  9. Center for Disease Control: Revision of the case definition of acquired immunodeficiency syndrome for national reporting—United States. MMWR 34:373, 1985

    Google Scholar 

  10. Portaro JK, Britton S, Ash LR: Brugia pahangi: Depressed mitogen reactivity in filarial infections in the jird, Meriones ungulatus. Exp Parasitol 40:438–446, 1976

    Google Scholar 

  11. Boyum A: Separation of lymphocytes from blood and bone marrow. Scand J Clin Lab Invest 21 (Suppl 97):77–89, 1968

    Google Scholar 

  12. Jondal M, Spina CA, Targan S: Human spontaneous killer cells: Selective cytotoxicity against tumor-derived target cells. Nature 272:62–64, 1978

    Google Scholar 

  13. Jackson AL, Warner NL: Preparation, staining, and analysis by flow cytometry of peripheral blood leukocytes.In Manual of Clinical Laboratory Immunology, N Rose, H Friedman, JL Fahey (eds). Washington, DC, American Society for Microbiology, 1986, pp 226–235

    Google Scholar 

  14. Lanier LL, Engleman EG, Gatenby P, Babcock GF, Warner NL, Herzenberg LA: Correlation of functional properties of human lymphoid cell subsets and surface marker phenotypes using multiparameter analyses and flow cytometry. Immunol Rev 74:143–160, 1983

    Google Scholar 

  15. Clement LT, Grossi CE, Gartland GL: Morphologic and phenotypic features of the subpopulation of Leu2+ cells that suppresses B cell differentiation. J Immunol 133:2461–2468, 1984

    Google Scholar 

  16. Fahey JL, Prince H, Weaver M, Groopman J, Visscher B, Schwartz K, Detels R: Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Am J Med 76:95–100, 1984

    Google Scholar 

  17. Creemers PC, Stark DF, Boyko WJ: Evaluation of natural killer cell activity in patients with persistent generalized lymphadenopathy and acquired immunodeficiency syndrome. Clin Immunol Immunopathol 36:141–150, 1985

    Google Scholar 

  18. Ruscetti RW, Mikovits JA, Kalyanaraman VS, Overton R, Stevenson H, Stromberg K, Herberman RB, Farrar WI, Ortaldo JR: Analysis of effector mechanisms against HTLV-I and HTLV III/LAV-infected lymphoid cells. J Immunol 136:3619–3624, 1986

    Google Scholar 

  19. Rook AH, Hooks JJ, Quinnan GV, Lane HC, Manischewitz JF, Macher AM, Masur H, Fauci AS, Djeu JY: Interleukin-2 enhances the natural killer cell activity of acquired immune deficiency syndrome patients through a gamma-interferon-independent mechanism. J Immunol 134:1503–1507, 1985

    Google Scholar 

  20. Reddy M, Pinyavat N, Grieco MH: Interleukin 2 augmentation of natural killer cell activity in homosexual men with acquired immune deficiency syndrome. Infect Immun 44:339–343, 1984

    Google Scholar 

  21. Bonavida B, Katz J, Gottlieb M: Mechanism of diminished NK activity in patients with acquired immune deficiency syndromes: Localization of the NK defect in the trigger involved in the release of NKCF by the stimulator target. Nat Immun Cell Growth Regul 4:239, 1985

    Google Scholar 

  22. Stites DP, Casavant CH, McHugh TM, Moss AR, Beal SL, Ziegler JL, Saunders AM, Warner NL: Flow cytometric analysis of lymphocyte phenotypes in AIDS using monoclonal antibodies and simultaneous dual immunofluorescence. Clin Immunol Immunopathol 38:161–177, 1986

    Google Scholar 

  23. Afrasiabi R, Mitsuyasu RT, Nishanian P, Martinez-Maza O, Fahey JL: Characterization of a distinct subgroup of high risk individuals with Kaposi's sarcoma with good prognosis who present with normal T4 cell numbers and T4:T8 ratio and negative HTLV-III serology. Am J Med (in press), 1986

  24. Phillips JH, Lanier LL: Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol 136:1579–1585, 1986

    Google Scholar 

  25. Biron C, Natuk RJ, Welsh RM: Generation of large granular T lymphocytesin vivo during viral infection. J Immunol 136:2280–2286, 1986

    Google Scholar 

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Plaeger-Marshall, S., Spina, C.A., Giorgi, J.V. et al. Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS). J Clin Immunol 7, 16–23 (1987). https://doi.org/10.1007/BF00915420

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