Natural killing activity in sjögren's syndrome
N. Miyasaka MD
Assistant Professor of Medicine, UTHSCSA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Dr. Miyasaka is an Arthritis Foundation Postdoctoral Fellow
Search for more papers by this authorW. Seaman MD
Assistant Professor of Medicine, UCSF
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorA. Bakshi MD
Research Associate
National Institutes of Health, Bethesda, MD
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorB. Sauvezie MD
Hopital Saint-Jacques, Clermont-Ferrand, France
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorV. Strand MD
San Francisco, CA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorR. Pope MD
Associate Professor, UTHSCSA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorCorresponding Author
N. Talal MD
Professor of Medicine and Microbiology
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78284Search for more papers by this authorN. Miyasaka MD
Assistant Professor of Medicine, UTHSCSA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Dr. Miyasaka is an Arthritis Foundation Postdoctoral Fellow
Search for more papers by this authorW. Seaman MD
Assistant Professor of Medicine, UCSF
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorA. Bakshi MD
Research Associate
National Institutes of Health, Bethesda, MD
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorB. Sauvezie MD
Hopital Saint-Jacques, Clermont-Ferrand, France
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorV. Strand MD
San Francisco, CA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorR. Pope MD
Associate Professor, UTHSCSA
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Search for more papers by this authorCorresponding Author
N. Talal MD
Professor of Medicine and Microbiology
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas, and the Immunology/Arthritis Section, Veterans Administration Hospital at San Francisco, The University of California, San Francisco, California.
Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78284Search for more papers by this authorAbstract
Natural killing (NK) by peripheral blood mono-nuclear cells (PBMC) against K562 cells was examined in 27 patients with Sjögren's syndrome and 17 normal controls. NK activity in the patients was significantly reduced compared with normal controls (34.6 ± 3.4% versus 52.2 ± 3.4%, P < 0.001). Patients with secondary Sjögren's had lower cytotoxicity compared with those who had primary Sjögren's (28.5 ± 5.5% versus 37.3 ± 4.2%, P < 0.01). The proportion of PBMC with characteristics of NK cells was not decreased in the patients. NK by normal PBMC was diminished both in the presence of sera from patients with reduced NK and when the effector cells were pretreated with the sera. Pretreatment of target K562 cells did not alter NK activity. Suppression of NK by sera from patients did not correlate with levels of immune complexes or with antilymphocyte antibodies. Some patients had adherent cells which inhibited NK function. Addition of either indomethacin or catalase partially restored NK activity in such patients, indicating that both prostaglandins and hydrogen peroxide play a role in suppression. These data suggest that multiple mechanisms are involved in the defective NK activity seen in patients with Sjögren's syndrome. The reduction of NK activity in Sjögren's syndrome may contribute to the increased incidence of lymphoid malignancy.
References
- 1 Strand V, Talal N: Advances in the diagnosis and concepts of Sjogren's syndrome (autoimmune exocrinopathy). Bull Rheum Dis 30: 1046–1049, 1981
- 2 Talal N, Sylvester RA, Daniel TE, Greenspan JS, Williams RC Jr: T and B lymphocytes in peripheral blood and tissue lesions in Sjogren's syndrome. J Clin Invest 53: 180–189, 1974
- 3 Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR, Costa J, Decker JL, Chused TM: Increased risk of lymphoma in sicca syndrome. Ann Intern Med 89: 888–892, 1978
- 4 RB Herberman, editor: Natural Cell-Mediated Immunity Against Tumors. New York, Academic Press, 1980
- 5 Timonen T, Ortaldo JR, Herberman RB: Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153: 569–582, 1981
- 6 Herberman RB, Nunn MS, Holdern HT, Laurin DH: Natural cytotoxicity reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer 16: 230–239, 1975
- 7 Kasai M, Yoneda T, Habu S, Maruyama Y, Okumura K, Tokunaga T: In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature (London) 291: 334–335, 1981
- 8 Haller O, Hansson M, Kiessling R, Wigzell H: Role of non-conventional natural killer cells in resistance against syngeneic tumor cells in vivo. Nature (London) 270: 609–611, 1977
- 9 Roder JC: The beige mutation in the mouse. I. A stem cell predetermined impairment on natural killer cell function. J Immunol 123: 2168–2173, 1979
- 10 Haliotis T, Roder J, Klein M, Ortaldo J, Fauci AS, Herberman RB: Chediak-Higashi gene in humans. I. Impairment of natural killer function. J Exp Med 151: 1038–1048, 1980
- 11 Saxena RK, Saxena DB, Saler WH: Defective T-cell response in beige mice. Nature 295: 240–241, 1982
- 12 Goto M, Tanimoto K, Chihara T, Horiuchi Y: Natural cell-mediated cytotoxicity in Sjogren's syndrome and rheumatoid arthritis. Arthritis Rheum 24: 1377–1382, 1981
- 13 Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9: 175–176, 1958
- 14 Cohen AS, Reynolds WE, Franklin EC, Kulka JP, Shulman LE, Wallace SL: Preliminary criteria for the classification of systemic lupus erythematosus. Bull Rheum Dis 21: 643–648, 1971
- 15 Miyasaka N, Sauvezie B, Pierce DA, Daniels TE, Talal N: Decreased autologous mixed lymphocyte reaction in Sjogren's syndrome. J Clin Invest 66: 928–932, 1980
- 16 Ackerman SK, Douglas SD: Purification of human monocytes on microexudate-coated surfaces. J Immunol 120: 1372–1374, 1978
- 17 Seaman WE, Gindhart TD, Blackman MA, Dalal B, Talal N, Werb Z: Natural killing of tumor cells by human peripheral blood cells: suppression of killing in vitro by tumor promoting phorbol diesters. J Clin Invest 67: 1324–1333, 1981
- 18 Ledbetter JA, Evans RL, Lipinski M, Cunningham C, Good RA, Herzenberg LA: Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med 153: 110–115, 1981
- 19 Howard FD, Ledbetter JA, Wong J, Bieber CP, Stinson EB, Herzenberg LA: A human T lymphocyte differentiation marker defined by monoclonal antibodies which block E-rosette formation. J Immunol 126: 2117–2120, 1981
- 20 Breard J, Reinherz EL, Kung PC, Goldstein G, Schlossman SF: A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol 124: 1943–1948, 1980
- 21 Yoshinoya S, Pope RM: Detection of immune complexes in acute rheumatic fever and their relationship to HLA-B5. J Clin Invest 65: 136–145, 1980
- 22 Terasaki PI, Mottironi BD, Barnett EV: Cytotoxins in disease: autocytotoxins in lupus. N Engl J Med 283: 724–727, 1970
- 23 Bakshi A, Miyasaka N, Kavathas P, Daniels TE, Herzenberg LA, Talal N: Lymphocyte subsets in Sjogren's syndrome: a quantitative analysis using monoclonal antibodies and the fluorescence-activated cell sorter. J Clin Lab Immunol (in press)
- 24 Lawley TJ, Moutsopoulos HM, Katz SI, Theofilopoulos H, Chused TM, Frank MM: Demonstration of circulating immune complexes in Sjogren's syndrome. J Immunol 123: 1382–1387, 1979
- 25 Fischbach M, Char D, Christensen M, Daniels T, Whaley K, Alspaugh M, Talal N: Immune complexes in Sjogren's syndrome. Arthritis Rheum 23: 791–795, 1980
- 26 West WH, Cannon GB, Kay HD, Bonnard GD, Herberman RB: Natural cytotoxicity reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells. J Immunol 118: 355–361, 1977
- 27 Breard J, Reinherz EL, O'Brien C, Schlossman SF: Delineation of an effector population responsible for natural killing and antibody-dependent cellular cytotoxicity in man. Clin Immunol Immunopathol 18: 145–150, 1981
- 28 Abo T, Roder JC, Abo W, Cooper MD, Balch CM: Natural killer (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology. J Clin Invest 70: 193–197, 1982
- 29 Katz P, Zaytoun AM, Fauci AS: Deficiency of active natural killer cells in Chediak-Higashi syndrome: localization of the defect using a single cell cytotoxicity assay. J Clin Invest 69: 1231–1238, 1982
- 30 Sulica A, Gherman M, Galatiuc C, Manciulea M, Herberman RB: Inhibition of human natural killer cell activity by cytophilic immunoglobulin G. J Immunol 128: 1031–1036, 1982
- 31 Bonney RJ, Naruns P, Davies P, Humes JL: Antigen-antibody complexes stimulate the synthesis and release of prostaglandins by mouse peritoneal macrophages. Prostaglandins 18: 606–616, 1979
- 32 Nair PNM, Fernandes G, Onoe K, Day NK, Good RA: Inhibition of effector cell functions in natural killer cell activity (NK) and antibody-dependent cellular cytotoxicity (ADCC) in mice by normal and cancer sera. Int J Cancer 25: 667–677, 1980
- 33 Ehrlich R, Efrati M, Witz IP: Cytotoxicity and cytostasis mediated by splenocytes of mice subjected to chemical carcinogens and of mice bearing primary tumors, Natural Cell-Mediated Immunity Against Tumors. Edited by RB Herberman. New York, Academic Press, 1980, pp 997–1010
- 34 Cudkowicz G, Hochman PS: Do natural killer cells engage in regulated reactions against self to ensure homeostasis?*. Immunol Res 44: 13–41, 1979
- 35 Johnston RB, Godzik CA, Cohn ZA: Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 148: 115–127, 1978
- 36 Stadecker MJ, Calderon J, Karnovsky ML, Unanue ER: Synthesis and release of thymidine by macrophages. J Immunol 119: 1738, 1977
- 37 Grimm W, Seitz M, Kirchner H, Gemsa D: Prostaglandin synthesis in spleen cell cultures of mice injected with Corynebacterium parvum. Cell Immunol 40: 419–426, 1978
- 38 Kiessling R, Hochman PS, Haller O, Shearer GM, Wigzell H, Cudkowicz G: Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol 7: 655–663, 1977
- 39 Metzger Z, Hoffeld JT, Oppenheim JJ: Macrophage-mediated suppression. I. Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J Immunol 124: 983–988, 1980
- 40 Seaman WL, Gindhardt TD, Blackman MA, Dalal B, Talal N, Werb Z: Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes: requirement for reactive metabolites of oxygen. J Clin Invest 69: 876–888, 1982
- 41 Droller MJ, Schneider MU, Perlmann P: A possible role of prostaglandins in the inhibition of natural and antibody-dependent cell-mediated cytotoxicity against tumor cells. Cell Immunol 39: 165–177, 1978
- 42 Brunda MJ, Herberman RB, Holden HT: Inhibition of murine natural killer cell activity by prostaglandins. J Immunol 124: 2682–2687, 1980
