Abstract
Knowledge concerning the roles of iron and iron binding proteins in lymphocyte physiology and pathology has developed rapidly over the last few years. The genes for the major iron binding proteins have been cloned and sequenced and are now being studied with respect to transcriptional and posttranscriptional regulatory mechanisms. T cells, B cells, macrophages, and natural killer cells appear to differ from one another in the ways in which they synthesize and utilize iron binding proteins and in the amount of iron they take up and store. This suggests that differential modulation of iron-dependent metabolic functions is an intrinsic part of the distinctive physiology of each cellular component of the immune system and that the distribution of iron between those components is a carefully managed facet of the immune response. Since the immune response does not seem to be dramatically impaired by alterations in iron supplies that adversely affect other organs, it may well be that the cells of the immune system are especially adapted to have both high-priority access to iron when supply is low and high-level protection against iron-related toxicity when supply is in excess.
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References
Pietrangelo A, Rocchi E, Casalgrandi G, Rigo G, Ferrari A, Perini M, Ventura E, Cairo G: Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum. Gastroenterology 102(3):1071–1073, 1992
Lombard M, Bomford AB, Polson RJ, Bellingham AJ, Williams R: Differential expression of transferrin receptor in duodenal mucosa in iron overload. Evidence for a site-specific defect in genetic hemochromatosis. Gastroenterology 98(4):976–984, 1990
Chasteen ND: The identification of the probable locus of iron and anion binding in the transferrins. Trends Biochem Sci 8:272–275, 1983
Young SP, Bomford AB, Williams R: The effect of the iron saturation of transferrin on its binding and uptake by rabbit reticulocytes. Biochem J 219:505–510, 1984
Jing S, Trowbridge IA: Identification of the intermolecular disulphide bonds of the human transferrin receptor and its lipid-attachment site. EMBO J 6:327–331, 1987
Trowbridge IS, Newman RA, Domingo DL, Sauvage C: Transferrin receptors: Structure and function. Biochem Pharmacol 33(6):925–932, 1984
Do SI, Enns C, Cummings RD: Human transferrin receptor contains O-linked oligosaccharides. J Biol Chem 265(1):114–125, 1990
Trowbridge IA, Collawn J, Shuqian Jing, White S, Esekogwu V, Stangel M. Structure-function analysis of the human transferrin receptor: Effects of antireceptor monoclonal antibodies on tumor growth. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol 58, pp 139–147, 1991
Morgan EH, Baker E: Role of transferrin receptors and endocytosis in iron uptake by hepatic and erythroid cells. Ann NY Acad Sci 526:65–82, 1988
Dautry-Varsat A, Ciechanover A, Lodish HF: pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 80:2258–2262, 1983
Nilsen T, Romslo I: Subcellular localization of transferrin and pyrophosphate in liver cells after perfusionin situ or incubationin vitro. Scand J Clin Lab Invest 52(5):373–378, 1992
Reichard P, Ehrenberg A: Ribonucleotide reductase—A radical enzyme. Science 221:514–519, 1983
Thelander L, Gräslund A, Thelander M: Continual presence of oxygen and iron required for mammalian ribonucleotide reduction: Possible regulation mechanism. Biochem Biophys Res Comm 110(3):859–865, 1983
Wharton M, Granger DL, Durack DT: Mitochondrial iron loss from leukemia cells injuryed by macrophages. J Immunol 141:1311–1317, 1988
Nelson MJ, Batt DG, Thompson JS, Wright SW: Reduction of the active-site iron by potent inhibitors of lipoxygenases. J Biol Chem 266(13):8225–8229, 1991
Bomford AB, Munro HN: Ferritin gene expression in health and malignancy. Pathology 60:10–18, 1992
Arosio P, Levi S, Santambrogio P, Cozzi A, Luzzago A, Cesareni G, Albertini A: Structural and functional studies of human ferritin H and L chains. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol 58, pp 127–131
Ford GC, Harrison PM, Rice DW, Smith JMA, Treffry A, White JL, Yariv J: Ferritin: Design and function of an iron-storage molecule. Phil Trans R Soc Lond B304:551–565, 1984
Fargion S, Fracanzani AL, Cislaghi V, Levi S, Cappellini MD, Fiorelli G: Characteristics of the membrane receptor for human H-ferritin. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol. 58, pp 164–170
Klausner RD, Harford JB: Cis-trans models for posttranscriptional gene regulation. Science 246:870–872, 1989
Haile DJ, Rouault TA, Tang CK, Chin J, Harford JB, Klausner RD: Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: Role of the iron-sulfur cluster. Proc Natl Acad Sci USA 89(16):7536–7540, 1992
Masson PL, Heremans JF, Schonne E: Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med 130:643, 1969
Broxmeyer HE, Mantel C, Gentile P, Srivastave C, Miyazawa K, Zucali JR, Rado TA, Levi S, Arosio P: Actions of H-subunit ferritin and lactoferrin as suppressor molecules of myelopoiesisin vitro andin vivo. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol 58, pp 178–181
Brown JP, Hewick RW, Hellstrom I, Hellstrom KE, Doolittle RF, Dreyer WJ: Human melanoma-associated antigen p97 is structurally and functionally related to transferrin. Nature 296:171–173, 1982
Brown JP, Woodbury RG, Hart CE, Hellström I, Hellström KE: Quantitative analysis of melanoma-associated antigen p97 in normal and neoplastic tissues. Proc Natl Acad Sci USA 78(1):539–543, 1981
Jensen C, Burgart L, Stewart B, Naumann P, Kemp J: Melanotransferrin (p97): Flow cytometric studies of expression and regulation in B lymphoblastoid cell lines and immunohistochemical studies of expression in brain vasculature. Lab Invest 66(1):107A, 1922
Garratt RC, Jhoti H: A molecular model for the tumour-associated antigen, p97, suggests a Zn-binding function. FEBS Lett 305(1):55–61, 1992
Krönke M, Leonard WJ, Depper JM, Greene WC: Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med 161:1593–1598, 1985
Weiel JE, Hamilton TA: Quiescent lymphocytes express intracellular transferrin receptors. Biochem Biophys Res Comm 119(2):598–602, 1984
Neckers LM, Cossman J: Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci USA 80:3494, 1983
Kumagai N, Benedict SH, Mills GB, Gelfand EW: Comparison of phorbol ester/calcium ionophore and phytohe-magglutinin-induced signaling in human T lymphocytes. J Immunol 140(1):37–43, 1988
Quyand Q, Miskimins WK: A supercoil-dependent structural alteration within the regulatory region of the human transferrin receptor gene. Biochem Biophys Res Comm 183(1):62–69, 1992
Pelosi-Testa E, Samoggia P, Giannella G, Montesoro E, Caravita T, Salvo G, Camagna A, Isacchi G, Tests U, Peschle C: Mechanisms underlying T-lymphocyte activation: Mitogen initiates and IL-2 amplifies the expression of transferrin receptors via intracellular iron level. Immunology 64:273–279, 1988
Lum JB, Infante AJ, Makker DM, Yang F, Bowman BH: Transferrin synthesis by inducer T lymphocytes. J Clin Invest 77:841–849, 1986
Thorson JA, Smith KM, Gomez F, Naumann PW, Kemp JD: Role of iron in T cell activation: TH1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IgG Mabs against the transferrin receptor and the iron chelator deferoxamine. Cell Immunol 134(1):126–137, 1991
Kemp JD, Thorson JA, Gomez F, Smith KM, Cowdery JS, Ballas ZK: Inhibition of lymphocyte activation with anti-transferrin receptor Mabs: A comparison of three reagents and further studies of their range of effects and mechanism of action. Cell Immunol 122(1):218–230, 1989
Weber RJ, Finkelman FD: Increased expression of the B lymphocyte receptor for transferrin is stimulated byin vivo cross-linking of cell surface IgD. Cell Immunol 104:400, 1987
Futran J, Kemp JD, Field EH, Vora A, Ashman RF: Transferrin receptor synthesis is an early event in B cell activation. J Immunol 143:787–792, 1989
Neckers LM, Yenokida G, James SP: The role of the transferrin receptor in human B lymphocyte activation. J Immunol 133:2437, 1984
Thorson JA: Iron, Transferrin, and the Transferrin Receptor in Lymphocyte Growth: Studies with an Anti-Transferrin Receptor Monoclonal Antibody, Doctoral thesis, Department of Microbiology, University of Iowa, 1992
Lederman HM, Cohen A, Lee JWW, Freedman MH, Gelfand EW: Deferoxamine: A reversible S-phase inhibitor of human lymphocyte proliferation. Blood 64:748, 1984
Hirata T, Bitterman PB, Mornex JF, Crystal RG: Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation. J Immunol 136(4):1339–1345, 1986
Testa U, Petrini M, Quarnata MT, Pelosi-Testa E, Mastroberardino G, Camagna A, Boccoli G, Sargiacomo M, Isacchi G, Cozzi A, Arosio P, Peschle C: Iron upmodulates the expression of transferrin receptors during monocyte-macrophage maturation. J Biol Chem 264:13181–13187, 1989
Testa U, Petrini M, Quaranta MT, Pelosi E, Kühn L, Peschle C: Differential regulation of iron-responsive element-binding protein in activated lymphocytes versus monocytes-macrophages. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol 58, pp 158–163
Wei Y, Miller SC, Tsuji Y, Torti SV, Torti FM: Interleukin 1 induces ferritin heavy chain in human muscle cells. Biochem Biophys Res Comm 169(1):289–296, 1990
Alvarez-Hernández X, Licéaga J, McKay IC, Brock JH: Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor. Lab Invest 61(3):319–322, 1989
Reif DW, Simmons RD: Nitric oxide mediates iron release from ferritin. Arch Biochem Biophys 283(2):537–541, 1990
London L, Perussia B, Trinchieri G: Induction of proliferationin vitro of resting human natural killer cells: Expression of surface activation antigens. J Immunol 134(2):718–727, 1985
Vodinelich L, Sutherland R, Schneider C, Newman R, Greaves M: Receptor for transferrin may be a “target” structure for natural killer cells. Immunology 80:835–839, 1983
Baines MG, Lafleur FL, Holbein BE: Involvement of transferrin and transferrin receptors in human natural killer effector: target interaction. Immunol Lett 7:51–55, 1983
Newman RA, Warner JF, Dennert G: NK recognition of target structures: Is the transferrin receptor the NK target structure? J Immunol 133(4):1841–1845, 1984
Lopez-Guerrero JA, Redondo JM, Alarcon B, Sanchez-Madrid F, Rodriguez-Moya M, Ortiz-de-Landazuri M, Bernabeu C, Fresno M: Different functional domains on the transferrin receptor molecule defined by monoclonal antibodies. Immunology 66(2):252–257, 1989
Dokhélar MC, Garson D, Testa U, Tursz T: Target structure for natural killer cells: Evidence against a unique role for transferrin receptor. Eur J Immunol 14:340–344, 1984
Benoist H, Comoe L, Joly P, Carpentier Y, Desplaces A Dufer J: Comparative effect of fagaronine, adriamycin and aclacinomycin on K562 cell sensitivity to natural-killer-mediated lysis. Lack of agreement between alteration of transferrin receptor and CD15 antigen expressions and induction of resistance to natural killer. Cancer Immunol Immunother 30(5):289–294, 1989
Bridges KR, Smith BR: Discordance between transferrin receptor expression and susceptibility to lysis by natural killer cells. J Clin Invest 76(3):913–918, 1985
Salmon M, Bacon PA, Young SP: Natural killer cells in peripheral blood and the mixed lymphocyte response: Interaction with the transferrin receptor. Immunology 62(1):81–87, 1987
Perl A, Looney RJ, Ryan DH, Abraham GN: The low affinity 40,000 Fc gamma receptor and the transferrin receptor can be alternative or simultaneous target structures on cell sensitive for natural killing. J Immunol 136(12):4714–4720, 1986
Storkus WJ, Dawson JR: B cell sensitivity to natural killing: correlation with target cell stage of differentiation and state of activation. J Immunol 136(5):1542–1547, 1986
Rieber EP, Rank G, Riethmuller G: Transferrin receptors on tumor and bone marrow cells: Lack of involvement as target structure for natural killer cells. Kin Wochenschr 31(21):1119–1123, 1986
Borysiewicz LK, Graham S, Sissons JG: Human natural killer cell lysis of virus-infected cells. Relationship to expression of the transferrin receptor. Eur J Immunol 16(4):405–411, 1986
Tazzari PL, Zauli D, Raspadori D, Crespi C, Magnani M, Tassinari A, Gobbi M: Role of target and effector cell structures in natural killer-mediated cytotoxicity. Ric Clin Lab 16(3):443–447, 1986
Joynson DHM, Jacob A, Walker DM, Dalby AE: Defect of cell-mediated immunity in patients with iron-deficiency anaemia. Lancet 2:1058, 1972
MacDougall LG, Anderson R, McNab GM, Katz J: The immune response in iron deficient children: Impaired cellular defense mechanisms with altered humoral components. J Pediat 86:833, 1975
Bhaskaram P, Reddy V: Cell-mediated immunity in iron and vitamin deficient children. Br Med J 3:522, 1975
Chandra RK, Saraya AK: Impaired immuno-competence associated with iron deficiency. J Pediat 86:899–901, 1975
Fletcher J, Mather J, Lewis MJ, Withing G: Mouth lesions in iron-deficient anemia: Relationship to Candida albicans in saliva and to impairment of lymphocyte transformation. J Infect Dis 131:44–50, 1975
Krantman HJ, Yound SR, Ank BJ, O'Donnel MC, Rachelefsky GS, Stiehman RE: Immune function in pure iron deficiency. Am J Dis Child 136:840–844, 1982
Sawitsky B, Knater R, Sawitsky A: Lymphocyte response to phytomitogens in iron deficiency. Am J Med Sci 277:153–160, 1976
Galan P, Thibault H, Preziosi P, Hercberg S: Interleukin 2 production in iron-deficient children. Biol Trace Elem Res 32:421–426, 1992
Kuvibidila S, Dardenne M, Savino W, Lepault F: Influence of iron-deficiency anemia on selected thymus functions in mice: Thymulin biological activity, T-cell subsets, and thymocyte proliferation. Am J Clin Nutr 51:228–232, 1990
Kuvibidila SR, Baliga BS, Suskind RM: Effects of iron deficiency anemia on delayed cutaneous hypersensitivity in mice. Am J Clin Nutr 34:2635–2640, 1981
Baliga BS, Kuvibidila SR, Susking RM: Effect of iron deficiency on the cell mediated immune response. Ind J Pediat 49:431–445, 1982
Kuvibidila SR, Baliga BS, Suskind RM: Generation of plaque forming cells in iron deficient anemic mice. Nutr Rep Int 26:861–870, 1982
Kuvibidila SR: Effects of moderate and severe iron deficiency anemia on mitogenic response of lymphocytes from mice spleen and lymph nodes. Acta Pharmacol Toxicol (Suppl)59:122–125, 1985
Blakely BR, Hamilton DL: The effect of iron deficiency on the immune response in mice. Drug Nutr Interact 5(4):249–255, 1988
Dhur A, Galan P, Hannoun C, Hout K, Hercberg S: Effects of iron deficiency upon the antibody response to influenza virus in rats. J Nutr Biochem 1:629–634, 1990
Chandra RK, Newberne PM: Nutrition Immunity and Infections. New York, Plenum, 1977, pp 67–126
Kuvibidila S, Wade S: Macrophage function as studied by the clearance of 125I-labeled polyvinylpyrrolidone in iron-deficient and iron-replete mice. J Nutr 117(1):170–176, 1987
Moore LL, Humbert JR: Neutrophil bactericidal dysfunction towards oxidant radical-sensitive microorganisms during experimental iron deficiency. Pediat Res 18:789–791, 1984
Spear AT, Sherman AR: Iron deficiency alters DMBA-induced tumor burden and natural killer cell cytotoxicity in rats. J Nutrit 122(1):46–55, 1992
Djeha A, Brock JH: Uptake and intracellular handling of iron from transferrin and iron chelates by mitogen stimulated mouse lymphocytes. Biochim Biophys Acta 1133:147–152, 1992
Rudd MJ, Good MF, Chapman DE, Powell LW, Halliday JW: Clonal analysis of the effect of iron on human cytotoxic and proliferating T lymphocytes. Immunol Cell Biol 68:317–324, 1990
Good MR, Powell LW, Halliday JW: The effect of non-transferrin-bound iron on murine T lymphocyte subsets: Analysis by clonal techniques. Clin Exp Immunol 70:164–172, 1987
Djeha A, Brock JH: Effect of transferrin, lactoferrin and chelated iron on human T lymphocytes. Br J Haematol 80(2):235–241, 1992
Nishiya K, de Sousa M, Tsoi E, Bognacki JJ, de Harven E: Regulation of expression of a human lymphoid cell surface marker by iron. Cell Immunol 53:71–83, 1980
Novogrodsky A, Suthanthiran M, Stenzel KH: Immune stimulatory properties of metalloporphyrins. J Immunol 143:3981–3987, 1989
Novogrodsky A, Suthanthiran M, Stenzel KH: Ferromitogens: Iron-containing compounds with lymphocyte-stimulatory properties. Cell Immunol 133:295–305, 1991
Akbar AN, Fitzgerald-Bocarsly PA, de Sousa M, Giardina PJ, Hilgartner MW, Grady RW: Decreased natural killer activity in thalassemia major: A possible consequence of iron overload. J Immunol 136(5):1635–1640, 1986
Kapadia A, de Sousa M, Markenson AL, Miller DR, Miller R, Good RA, Gupta S: Lymphoid cell sets and serum immunoglobulins in patients with thalassemia intermedia: Relationship to serum iron and splenectomy. Br J Haematol 45:405, 1980
Grady RW, Akbar AN, Giardina PJ, Hilgartner MW, de Sousa M: Disproportionate lymphoid cell subsets in thalassemia major: The relative contribution of transfusion and splenectomy. Br J Haematol 59:713, 1985
Abruzzo LV, Rowley DA: Homeostasis of the antibody response: Immunoregulation by NK cells. Science 222:581, 1983
Brieva JA, Stevens RH: Involvement of the transferrin receptor in the production of NK-induced suppression of human antibody synthesis. J Immunol 133:1288, 1984
Dhur A, Galan P, Hercberg S: Iron status, immune capacity and resistance to infections. Comp Biochem Physiol 94A(1):11–19, 1989
Strauss RG: Iron deficiency, infections, and immune function: A reassessment. Am J Clin Nutr 31:660–666, 1978
Hershko C, Peto TEA, Weatherall DJ: Iron and infection. Br Med J 296:660, 1988
Bullen JJ, Ward CG, Rogers HJ: The critical role of iron in some clinical infections. Eur J Clin Microbiol Infect Dis 10(8):613–617, 1991
Weinberg ED: Cellular iron metabolism in health and disease. Drug Metab Rev 22(5):531–579, 1990
Brock JH, de Sousa M: Immunoregulation by iron-binding proteins. Immunol Today 7(2):30, 1986
Dallman PR, Beutler E, Finch CA: Effects of iron deficiency exclusive of anemia. Br J Haematol 40:179–184, 1978
Oski FA: The nonhematologic manifestation of iron deficiency. Am J Dis Child 133:315–322, 1979
Lozoff B, Brittenham GM, Viteri FE, Wold AW, Urrutia J: Developmental deficients in iron-deficient infants: Effects of age and severity of iron lack. J Pediat 101:948–952, 1982
Cook JD, Lynch SR: The liabilities of iron deficiency. Blood 68:803–809, 1986
Sullivan JL: The iron paradigm of ischemic heart disease. Am Heart J 117:1177–1188, 1989
Cathcart MK, McNally AK, Morel DW, Chisolm III GM: Superoxide anion participation in human monocyte-mediated oxidation of low-density lipoprotein and conversion of low-density lipoprotein to a cytotoxin. J Immunol 142:1963–1969, 1989
Kochan I: The role of iron in bacterial infections with special consideration of host-tubercle bacillus interaction. Curr Top Microbiol Immunol 60:1–30, 1973
Taylor AE, Matalon S, Ward P (eds): Physiology of Oxygen Radicals. Baltimore, Williams & Wilkins, 1986
Breedveld FC, Dynesius-Trentham R: Collagen arthritis in the rats is initiated by CD4+ T cells and can be amplified by iron. Cell Immunol 121(1):1–12, 1989
Andrews FJ, Morris CJ, Lewis EJ, Blake DR: Effect of nutritional iron deficiency on acute and chronic inflammation. Ann Rheum Dis 46(11):859–865, 1987
Kaplan J, Jordan I, Sturrock A: Regulation of the transferrin-independent iron transport system in cultured cells. J Biol Chem 266(5):2997–3004, 1991
Seligman PA, Kovar J, Schleicher RB, Gelfand EW: Transferrin-independent iron uptake supports B lymphocyte growth. Blood 78(6):1526–1531, 1991
Alcantara O, Javors M, Boldt DH: Induction of protein kinase C mRNA in cultured lymphoblastoid T cells by iron-transferrin but not by soluble iron. Blood 77(6):1290–1297, 1991
Kuvibidila S, Baliga BS, Murthy KK: Impaired protein kinase C activation as one of the possible mechanisms of reduced lymphocyte proliferation in iron deficiency in mice. Am J Clin Nutr 54(5):944–950, 1991
Brock JH: The role of transferrin in lymphocyte transformation. Haematologia 17(2):187–198, 1984
Kovár J, Franek F: Growth-stimulating effect of transferrin on a hybridoma cell line: Relation to transferrin iron-transporting function. Exp Cell Res 182:358–369, 1989
Manger B, Weiss A, Hardy KJ, Stobo JD: A transferrin receptor antibody represents one signal for the induction of IL2 production by a human T cell line. J Immunol 136(2):532–538, 1986
Cano E, Pizarro A, Redondo JM, Sánchez-Madrid F, Bernabeu C, Fresno M: Induction of T cell activation by monoclonal antibodies specific for the transferrin receptor. Eur J Immunol 20:765–770, 1990
Toole-Simms W, Sun IL, Faulk WP, Löw H, Lindgren A, Crane FL, Morré DJ: Inhibition of transplasma membrane electron transport by monoclonal antibodies to the transferrin receptor. Biochem Biophys Res Comm 176(3):1437–1442, 1991
Bretscher MS: Cells can use their transferrin receptors for locomotion. Embo J 11(2):383–389, 1992
Fargion S, Fracanzani AL, Cislaghi V, Levi S, Cappellini MD, Fiorelli G: Characteristics of the membrane receptor for human H-ferritin. In Biotechnology of Plasma Proteins. Curr Stud Hematol Blood Transf, A Albertini, CL Lenfant, PM Mannucci, JJ Sixma (eds). Basel, Karger, 1991, Vol 58, pp 164–170
Fargion S, Fracanzani AL, Brando B, Arosio P, Levi S, Fiorelli G: Specific binding sites for H-ferritin on human lymphocytes: Modulation during cellular proliferation and potential implication in cell growth control. Blood 78(4):1056–1061, 1991
Broxmeyer HE, Cooper S, Levi S, Arosio P: Mutated recombinant human heavy-chain ferritins and myelosuppressionin vitro andin vivo: A link between ferritin ferroxidase activity and biological function. Proc Natl Acad Sci USA 88:770–774, 1991
Moroz C, Lahat N, Biniaminov M, Ramot G: Ferritin on the surface of lymphocytes in Hodgkin's disease patients. A possible blocking substance removed by levamisole. Clin Exp Immunol 29:30, 1977
Hann HWL, Stahlhut MW, Chung C: Inhibitory effect of isoferritins from tumor and non-tumor tissues on E-rosette formation. Lancet 1:43, 1984
Ramot B, Biniaminov M, Shohan C, Rosenthal E: Effect of levamisole on E-rosettes forming cellsin vivo andin vitro in Hodgkin's disease. N Engl J Med 294:809, 1976
Moroz C, Kupfer B: Suppressor cell activity of ferritin-bearing lymphocytes in patients with breast cancer. Isr J Med Sci 17:879, 1981
Pattanapanyasat K, Hoy TG, Jacobs A, Courtney S, Webster DJ: Ferritin-bearing T lymphocytes and serum ferritin in patients with breast cancer. Br J Cancer 57:193, 1988
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Kemp, J.D. The role of iron and iron binding proteins in lymphocyte physiology and pathology. J Clin Immunol 13, 81–92 (1993). https://doi.org/10.1007/BF00919264
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DOI: https://doi.org/10.1007/BF00919264