Abstract
Peripheral blood mononuclear cells (PBMC) from 16 non-institutionalized patients with Down syndrome (DS) were studied with various monoclonal antibodies and analysed for natural killer (NK), and NK-like activity. Lymphocyte proliferation and cytotoxic T-lymphocyte (CTL) cytotoxicity generated in mixed lymphocyte culture (MLC) were also evaluated in 11 DS patients. Phenotypic characterization of PBMC from DS subjects confirms our previous findings of high numbers of CD8+ lymphocytes and HNK-1+, and CD16+ cells. Lymphocyte proliferation and CTL cytotoxicity generated in MLC were low or absent in most patients. NK activity was low in almost all DS patients, while NK-like cytotoxicity generated in MLC was normal in the majority and did not correlate with NK activity from unstimulated PBMC.
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Abbreviations
- BSA:
-
bovine serum albumin
- DS:
-
Down syndrome
- CTL:
-
cytotoxic T lymphocytes
- FCS:
-
fetal calf serum
- MLC:
-
mixed lymphocyte culture
- NK:
-
natural killer
- PBMC:
-
peripheral blood mononuclear cells
- PBS:
-
phosphate-buffered saline
- PHA:
-
phytohaemagglutinin
References
Abo T, Cooper MD, Balch CM (1982) Characterization of HNK-1+ (Leu-7) human lymphocytes I. Two distinct phenotypes of human NK cells with different cytotoxic capability. J Immunol 129:1752–1757
Agarwal SS, Blumberg BS, Gerstlly BJS, London, WT, Sutmick J, Loeb LL (1970) DNA polymerase activity as an index of lymphocyte stimulation: studies in Down's syndrome. J Clin Invest 49: 161–169
Baxter R, Larkins RG, Martin FIR, Heyma P, Mylex K, Ryan L (1975) Down syndrome and thyroid function in adults. Lancet II: 794–796
Benda CE, Strassman GS (1965) The Thymus in mongolism. J Ment Defic Res 9:109–117
Bjorksten B, Back O, Gustavson KH, Hallmans G, Hagglof B, Tarnvik A (1980) Zinc and immune function in Down's syndrome. Acta Pediatr Scand 69:183–187
Boehmer H von, Turton K (1983) Autologous proliferating K/D restricted cytolytic T cell clones. Eur J Immunol 13:176–179
Boehmer H von, Kieselow P, Leiserson W, Haas W (1984) LYT-2-T cell-independent functions of LYT2+ cells stimulated with antigen or concanavalin A. J Immunol 133:59–64
Burgio GR, Severi F, Rossoni R, Vaccaro R (1965) Mongolism and thyroid autoimmunity. Lancet I:166–167
Burgio GR, Ugazio AG, Nespoli L, Marcioni AF, Bottelli AM, Pasquali F (1975) Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T and B cells markers in Down's syndrome at different ages. Eur J Immunol 5:600–603
Burgio GR, Lanzavecchia A, Maccario R, Vitiello A, Plebani A, Ugazio AG (1978) Immunodeficiency in Down's syndrome: T lymphocyte subset imbalance in trisomic children. Clin Exp Immunol 33:298–301
Burgio GR, Ugazio AG, Nespoli L, Maccario R (1983) Down syndrome: a model of immunodeficiency. Birth Defects 19:325–327
Cupples CG, Tan YH (1977) Effect of human interferon preparations on lymphoblastogenesis in Down's syndrome. Nature 267: 165–167
Duse M, Brugo MA, Martini A, Tassi C, Ferrario C, Ugazio AG (1980) Immunodeficiency in Down's syndrome: low levels of serum thymic factor in trisomic children. Thymus 2:123–131
Epstein LB, Epstein CJ (1980) T lymphocyte function and sensitivity to interferon in trisomy-21. Cell Immunol 51: 303–318
Fekete G, Kulcsar G, Daun P, Nasz I, Schuler D, Dobos M (1982) Immunological and virological investigations in Down's syndrome. Eur J Pediatr 138:59–62
Franceschi C, Licastro F, Paolucci P, Masi M, Cavicchi S, Zanotti M (1978) T and B lymphocyte subpopulations in Down's syndrome. A study on non-institutionalized subjects. J Ment Defic Res 22:179–191
Franceschi C, Licastro F, Chisicolo M, Bonetti F, Zanotti M, Fabris N, Macchegiani E, Fantini MP, Paolucci P, Masi M (1981) Deficiency of autologous mixed lymphocyte reaction and serum thymic factor levels in Down's syndrome. J Immunol 126:2161–2167
Funa K, Ameren G, Alm GV, Bjiorksten B (1984) Abnormal interferon production and NK cells responses to interferon in children with Down's syndrome. Clin Exp Immunol 56:493–500
Gaston JHS, Waer M (1985) Virus-specific MHC-restricted lymphocytes may initiate allograft rejection. Immunol Today 6:237–239
Gordon MC, Sinba SK, Carlson SD (1971) Antibody responses to influenza vaccine in patients with Down's syndrome. Am J Ment Defic 75:391–399
Griffith AW, Silvester PE (1967) Mongols and non-mongols compared in their response to active tetanus immunization. J Ment Defic Res 11:263–266
Gupta S, Fikzig SM, Mariano E, Quazi A (1983) Monoclonal antibody defined T cell subsets and autologous mixed lymphocyte reaction in Down's syndrome. Clin Exp Immunol 53:25–30
Hansson M, Beran M, Andersson B, Kiessling R (1982) Inhibition of in vitro granulopoiesis by autologous allogeneic human NK cells. J Immunol 129:126–132
Herbermann RB (ed) (1980) Natural killer cell mediated immunity against tumors. Academic Press, New York
Herbermann RB, Ortaldo JR (1981) Natural killer cells: their role in defence against disease. Science 214:381–384
Hersey P, Bolhuis R (1987) “Non specific” MHC-unrestricted killer cells and their receptors. Immunol Today 8:233–239
James K, Ritchie AWS (1984) Do natural killer cells regulate B cell activity. Immunol Today 5:193–194
Kaplan J (1986) NK cell lineage and target specificity: a unifying concept. Immunol Today 7:10–13
Karttunen R, Nurmi T, Ilonen J, Surcel HM (1984) Cell-mediated immunodeficiency in Down's syndrome: normal IL-2 production but inverted ratio T-cell subsets. Clin Exp Immunol 55:257–263
Krivit W, Good RA (1957) Simultaneous occurrence of mongolism and leukemia. Ann J Dis Child 94:289–293
Lanier LL, Cwirla S, Federspiel N, Phillips JH (1986) Human natural killer cells isolated from peripheral blood do not rearrange T cell antigen receptor beta chain genes. J Exp Med 136:209–214
Levin S (1987) The immune system and susceptibility to infection in Down's syndrome. In: McCoy EE, Epstein CJ (eds) Oncology and immunology of Down syndrome. Liss, New York, pp 143–162
Levin S, Nir E, Hogilner BM (1975) T system immune deficiency in Down's syndrome. Pediatrics 56:123–126
Levin S, Schlesinger M, Handzel T, Hahn T, Altman Y, Czermobilsky B, Boss J (1979) Thymic deficiency in Down's syndrome. Pediatrics 63:80–86
Lopez V, Ochs HD, Thuline HC, Davis SD, Wedgwood RJ (1975) Defective antibody response to bacteriophage X174 in Down's syndrome. J Pediatr 86:207–211
Lopez-Botet M, Silva A, Rodriguez J, Landazuri MO (1982) Generation of T cell blasts with NK-like activity in human MLC: cellular precursors, IL-2 responsiveness, and phenotype expression. J Immunol 129:1109–1115
Maccario R, Ugazio AG, Nespoli L, Alberini C, Montagna D, Porta F, Bonetti F, Burgio GR (1984) Lymphocyte subpopulations in Down's syndrome: high percentage of circulating HNK-1+, Leu2a+ cells. Clin Exp Immunol 57:222–226
Maccario R, Burgio GR (1987) T and NK lymphocyte subpopulations in the neonate. In: Burgio GR, Hanson LA, Ugazio AG (eds) Immunology of the neonate. Springer, Berlin Heidelberg New York, pp 120–129
Miller RW (1970) Neoplasia and Down's syndrome. Ann NY Acad Sci 171:637–644
Moretta A, Pantaleo G, Mingari MC, Melioli G, Moretta L, Cerottini JC (1984) Assignment of human natural killer (NK) like cells to the T cell lineage. Single allospecific T cell clones lyse specific or NK-sensitive target cells via distinct recognition structures. Eur J Immunol 14:121–125
Morgensen KE, Vignaux F, Gresser I (1982) Enhanced expression of cellular receptors for human interferon alpha on peripheral lymphocytes from patients with Down's syndrome. FEBS 104:285–287
Morling N, Jakobsen BK, Platz P, Ryder LP, Svejgaard A, Thomsen M (1982) Typing for human alloantigens with the primed lymphocyte typing technique. Adv Immunol 32:66–156
Nair MPN, Schwartz SA (1984) Association of decreased T-cell-mediated natural cytotoxicity and interferon production in Down's syndrome. Clin Immunol Immunopathol 33:412–424
Nurmi T, Huttunen K, Lassila O, Hen Honen M, Sakkinen A, Linna SL, Tijlikainen A (1982) Natural killer cell function in trisomy-21 (Down's syndrome). Clin Exp Immunol 47:735–741
Ortaldo JR, Herbermann RB (1984) Heterogeneity of natural killer cells. Ann Rev Immunol 2:359–394
Oster J, Mikkelsen M, Nielsen A (1975) Mortality and life-table in Down's syndrome. Acta Paediatr Scand 64:322–326
Paciucci PA, McPhail S, Zarling JM, Bach FH (1980) Lysis of syngeneic solid tumor by alloantigen stimulated mouse T and non T cells. J Immunol 124:370–375
Parmiani G, Sensi M, Fossati G (1985) Allostimulation induced tumor cytotoxic cells: from mouse to man. Immunol Today 6: 215–218
Philip R, Berger AC, McNanus NH, Warner NH, Peacock MA, Epstein LB (1986) Abnormalities of the in vitro cellular and humoral responses to tetanus and influenza antigens with concomitant numerical alterations in lymphocyte subsets in Down syndrome (Trisomy-21). J Immunol 136:1661–1667
Phillips JH, Le AM, Lanier LL (1984) Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens. J Exp Med 159:993–1008
Pistoia V, Ghio R, Nocera A, Leprini A, Perata A, Ferrarini M (1985) Large granular lymphocytes have a promoting activity on human peripheral blood erythroid burst forming units. Blood 65: 464–472
Procopio ADG, Allavena P, Ortaldo JR (1985) Noncytotoxic functions of natural killer (NK) cells: large granular lymphocytes (LGL) produce a B cell growth factor (BCGF). J Immunol 135: 3264–3271
Revel M, Bash D, Ruddle FH (1976) Antibodies to cell surface components codes by human chromosome 21 inhibit action of interferon. Nature 260:139–141
Sasaki M, Obara Y (1969) Hypersensitivity of lymphocytes in Down's syndrome shown by mixed leucocyte culture experiments. Nature 222:596–598
Siegel M (1984) Susceptibility of mongoloids to infections. II. Antibody response to tetanus toxoid and typhoid vaccine. Ann J Hyg 48:63–73
Strassmann G, Bach FH, Zarling JM (1983) Depletion of human NK cells with monoclonal antibodies allows the generation of cytotoxic T lymphocytes without NK-like cells in mixed cultures. J Immunol 130:1556–1560
Strausser JL, Mazumder A, Grimm EA, Lotze MT, Rosemberg SA (1981) Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. J Immunol 127:266–271
Sutnik AI, London WT, Gerstly BJS, Cronlund MN, Blumberg BS (1968) Anicteric hepatitis associated with Australia antigen. JAMA 205:670–674
Tan YH (1975) Chromosome-21-dosage effect on inductibility of anti-viral gene (s). Nature 253:280–282
Tan HY (1976) Chromosome-21 and cell growth inhibitory effect of human interferon preparations. Nature 260:141–143
Ugazio AG, Burgio GR (1977) Immunodeficiency in Down's syndrome: relationship between presence of human thyroglobulin antibodies and HBsAg carries status. Eur J Pediatr 126:139–146
Walford RL, Gessett TC, Naeim F, Tam CF, Van Lauckes JL, Barnett EV, Chia D, Sparkes RS, Fahey JL, Spina C, Gatti RA, Media MA, Grossman H, Hibraur H, Motola M (1981) Immunological and biochemical studies of Down's syndrome as a model of accelerated aging. In: Segre D, Smith L (eds) Immunological aspects of aging. Dekker, New York, p 479
Weil J, Epstein LB, Epstein CJ (1980) Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays. J Interferon Res 1:111
Whittingham S, Pitt DB, Sharmay DLB, Mackay IR (1977) Stress deficiency of the T lymphocytes system exemplified by Down's syndrome. Lancet I:163–166
Widmer MB, Bach FH (1981) Antigen-driven helper cell-independent cloned cytolytic T lymphocytes. Nature 294:750–752
Yonagi Y, Caccia N, Kroanenberg M, Chin B, Roder J, Rohel D, Kiyohara T, Lanzon R, Toyonaga B, Rosenthal K, Dennert G, Acha-Orbea H, Hangartzer H, Hood L, Mark TW (1985) Gene rearrangement in cells with natural killer activity and expression of beta-chain of T-cell antigen receptor. Nature 314:631–633
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Montagna, D., Maccario, R., Ugazio, A.G. et al. Cell-mediated cytotoxicity in down syndrome: impairment of allogeneic mixed lymphocyte reaction, NK and NK-like activities. Eur J Pediatr 148, 53–57 (1988). https://doi.org/10.1007/BF00441815
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DOI: https://doi.org/10.1007/BF00441815