• 1
    Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17: 1426.
  • 2
    Ying S, Meng Q, Barata LT, Robinson DS, Durham SR, Kay AB. Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion molecule-1 expression, and the infiltration of eosinophils, macrophages, and T cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Immunol 1997; 158: 50507.
  • 3
    Akdis CA, Blaser K, Akdis M. Apoptosis in tissue inflammation and allergic disease. Curr Opin Immunol 2004; 16: 71723.
  • 4
    Trautmann A, Schmid-Grendelmeier P, Krüger K et al. T cells and eosinophils cooperate in the induction of bronchial epithelial apoptosis in asthma. J Allergy Clin Immunol 2002; 109: 32937.
  • 5
    Trautmann A, Akdis M, Brocker EB, Blaser K, Akdis CA. New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis. Trends Immunol 2001; 22: 5302.
  • 6
    Yssel H, Groux H. Characterization of T cell subpopulations involved in the pathogenesis of asthma and allergic diseases. Int Arch Allergy Immunol 2000; 121: 1018.
  • 7
    Trautmann A, Altznauer F, Akdis M, Simon HU, Disch R, Brocker EB, Blaser K, Akdis CA. The differential fate of cadherins during T-cell-induced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis. J Invest Dermatol 2001; 117: 92734.
  • 8
    Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, Akdis AC. A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IP-10, Mig and iTac for T cell chemotaxis towards epidermis in atopic dermatitis. J Immunol 2003; 171: 107884.
  • 9
    Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994; 265: 123740.
  • 10
    Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, De Vries JE, Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 73742.
  • 11
    Cottrez F, Hurst SD, Coffman RL, Groux H. T regulatory cells 1 inhibit a Th2-specific response in vivo. J Immunol 2000; 165: 484853.
  • 12
    Akdis M, Verhagen J, Taylor A et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004; 199: 156775.
  • 13
    Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K. Role of IL-10 in specific immunotherapy. J Clin Invest 1998; 102: 98106.
  • 14
    Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis AC. IL-10 and TGF-β cooperate in regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 2003; 33: 120514.
  • 15
    Lamb JR, Skidmore BJ, Green N, Chiller JM, Feldmann M. Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med 1983; 157: 143447.
  • 16
    Faith A, Akdis CA, Akdis M, Simon H-U, Blaser K. Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p56lck and ZAP-70 tyrosine kinase activities. J Immunol 1997; 159: 5360.
  • 17
    Schwartz RH. T cell anergy. Annu Rev Immunol 2003; 21: 30534.
  • 18
    Walker LS, Abbas AK. The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol 2002; 2: 1119.
  • 19
    Gershon RK, Kondo K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 1970; 18: 72337.
  • 20
    Levings MK, Sangregorio R, Galbiati F, Squadrone S, De Waal Malefyt R, Roncarolo MG. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 2001; 166: 55309.
  • 21
    Nasser SM, Ying S, Meng O, Kay AB, Ewan PW. Interleukin-10 levels increase in cutaneous biopsies of patients undergoing wasp venom immunotherapy. Eur J Immunol 2001; 31: 370413.
  • 22
    Akdis CA, Blaser K. IL-10-induced anergy in peripheral T cell and reactivation by microenvironmental cytokines: two key steps in specific immunotherapy. Faseb J 1999; 13: 6039.
  • 23
    Müller UR, Akdis CA, Fricker M, Akdis M, Bettens F, Blesken T, Blaser K. Successful immunotherapy with T cell epitope peptides of bee venom phospholipase A2 induces specific T cell anergy in bee sting allergic patients. J Allergy Clinimmunol 1998; 101: 74754.
  • 24
    Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 115164.
  • 25
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 3306.
  • 26
    Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+) CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295302.
  • 27
    Annunziato F, Cosmi L, Liotta F et al. Phenotype, localization, and mechanism of suppression of CD4+CD25+ human thymocytes. J Exp Med 2002; 196: 37987.
  • 28
    Wildin RS, Ramsdell F, Peake J et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 2001; 27: 1820.
  • 29
    Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome. J Clin Invest 2000; 106: R7581.
  • 30
    Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, Carr VA, Robinson DS. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004; 363: 60815.
  • 31
    Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 2001; 182: 20714.
  • 32
    Weiner HL. Oral tolerance for the treatment of autoimmune diseases. Annu Rev Med 1997; 48: 34151.
  • 33
    Hu D, Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 2004; 5: 51623.
  • 34
    Manavalan JS, Kim-Schulze S, Scotto L et al. Alloantigen specific CD8+ CD28– FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity. International Immunol 2004; 16: 105568.
  • 35
    Müller UR, Mosbech H. Position paper: Immunotherapy with hymenoptera venoms. Allergy 1993; 48: 3646.
  • 36
    Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. BMJ 1991; 302: 2659.
  • 37
    Jutel M, Watanabe T, Klunker S et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413: 4205.
  • 38
    Van Neerven RJ, Wikborg T, Lund G, Jacobsen B, Brinch-Nielsen A, Arnved J, Ipsen H. Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 1999; 163: 294452.
  • 39
    Rocklin RE, Sheffer A, Greineder DK, Melmon KL. Generation of antigen-specific suppressor cells during allergy desensitization. N Engl J Med 1980; 302: 121319.
  • 40
    Creticos PS, Adkinson NF Jr, Kagey-Sobotka A, Proud D, Meier HL, Naclerio RM, Lichtenstein LM, Norman PS. Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy. J Clin Invest 1985; 76: 224753.
  • 41
    Akdis CA, Akdis M, Blesken T, Wymann D, Alkan SS, Muller U, Blaser K. Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest 1996; 98: 167683.
  • 42
    Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 14151.
  • 43
    Carter L, Fouser LA, Jussif J et al. PD-1: PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol 2002; 32: 63443.
  • 44
    Kussebi F, Karamloo F, Rhyner C et al. A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy. J Allergy Clin Immunol 2005; 115: 3239.
  • 45
    Moore KW, De Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683765.
  • 46
    Enk AH, Saloga J, Becker D, Zadeh M, Knop J. Induction of hapten-specific tolerance by interleukin 10 in vivo. J Exp Med 1994; 179: 1397402.
  • 47
    Bacchetta R, Bigler M, Touraine JL et al. High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med 1994; 179: 493502.
  • 48
    Becker JC, Czerny C, Brocker EB. Maintenance of clonal anergy by endogenously produced IL-10. Int Immunol 1994; 6: 160512.
  • 49
    Mekala DJ, Alli RS, Geiger TL. IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+ CD25+ T lymphocytes. Proc Natl Acad Sci USA 2005; 102: 1181722.
  • 50
    Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S. Interleukin-10 regulation in normal subjects and patients with asthma. J Allergy Clin Immunol 1996; 97: 128896.
  • 51
    Koning H, Neijens HJ, Baert MR, Oranje AP, Savelkoul HF. T cells subsets and cytokines in allergic and non-allergic children. II. Analysis and IL-5 and IL-10 mRNA expression and protein production. Cytokine 1997; 9: 42736.
  • 52
    Pierkes M, Bellinghausen I, Hultsch T, Metz G, Knop J, Saloga J. Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells. J Allergy Clin Immunol 1999; 103: 32632.
  • 53
    Tillie-Leblond I, Pugin J, Marquette CH et al. Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus. Am J Respir Crit Care Med 1999; 159: 48794.
  • 54
    Makela MJ, Kanehiro A, Borish L et al. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proc Natl Acad Sci USA 2000; 97: 600712.
  • 55
    Yang X, Wang S, Fan Y, Han X. IL-10 deficiency prevents IL-5 overproduction and eosinophilic inflammation in a murine model of asthma-like reaction. Eur J Immunol 2000; 30: 38291.
  • 56
    Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998; 16: 13761.
  • 57
    Diebold RJ, Eis MJ, Yin M, Ormsby I, Boivin GP, Darrow BJ, Saffitz JE, Doetschman T. Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated. Proc Natl Acad Sci USA 1995; 92: 1221519.
  • 58
    Shull MM, Ormsby I, Kier AB et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992; 359: 6939.
  • 59
    Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25– naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198: 187586.
  • 60
    Huber S, Schramm C, Lehr HA et al. Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells. J Immunol 2004; 173: 652631.
  • 61
    Mamura M, Lee W, Sullivan TJ, Felici A, Sowers AL, Allison JP, Letterio JJ. CD28 disruption exacerbates inflammation in Tgf-beta1–/– mice. In vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-beta1. Blood 2004; 103: 4594601.
  • 62
    Chen Y, Inobe J, Kuchroo VK, Baron JL, Janeway CA Jr, Weiner HL. Oral tolerance in myelin basic protein T-cell receptor transgenic mice. Suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells. Proc Natl Acad Sci USA 1996; 93: 38891.
  • 63
    Vignola AM, Chanez P, Chiappara G et al. Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med 1997; 156: 5919.
  • 64
    Hellings PW, Vandenberghe P, Kasran A, Coorevits L, Overbergh L, Mathieu C, Ceuppens JL. Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway inflammation in genetically predisposed mice. Eur J Immunol 2002; 32: 58594.
  • 65
    Haneda K, Sano K, Tamura G, Shirota H, Ohkawara Y, Sato T, Habu S, Shirato K. Transforming growth factor-beta secreted from CD4(+) T cells ameliorates antigen-induced eosinophilic inflammation. A novel high-dose tolerance in the trachea. Am J Respir Cell Mol Biol 1999; 21: 26874.
  • 66
    Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000; 1: 16978.
  • 67
    Kulkarni AB, Huh CG, Becker D et al. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993; 90: 7704.
  • 68
    Sullivan TJ, Letterio JJ, Van Elsas A et al. Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation. Proc Natl Acad Sci USA 2001; 98: 258792.
  • 69
    Sung JL, Lin JT, Gorham JD. CD28 co-stimulation regulates the effect of transforming growth factor-beta1 on the proliferation of naive CD4+ T cells. Int Immunopharmacol 2003; 3: 23345.
  • 70
    Bright JJ, Sriram S. TGF-beta inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J Immunol 1998; 161: 17727.
  • 71
    Lin JT, Martin SL, Xia L, Gorham JD. TGF-beta 1 uses distinct mechanisms to inhibit IFN-gamma expression in CD4+ T cells at priming and at recall. Differential involvement of Stat4 and T-bet. J Immunol 2005; 174: 59508.
  • 72
    Durham SR, Walker SM, Varga EM et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999; 341: 46875.
  • 73
    Punnonen J, De Waal Malefyt R, Van Vlasselaer P, Gauchat J-F, De Vries JE. IL-10 and viral IL-10 prevent IL-4-induced IgE synthesis by inhibiting the accessory cell function of monocytes. J Immunol 1993; 151: 12809.
  • 74
    Sonoda E, Matsumoto R, Hitoshi Y et al. Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med 1989; 170: 141520.
  • 75
    Marshall JS, Leal-Berumen I, Nielsen L, Glibetic M, Jordana M. Interleukin (IL) -10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. J Clin Invest 1996; 97: 11228.
  • 76
    Schandene L, Alonso-Vega C, Willems F et al. B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 1994; 152: 436874.
  • 77
    Baxter AG, Hodgkin PD. Activation rules: the two-signal theories of immune activation. Nat Rev Immunol 2002; 2: 43946.
  • 78
    Boussiotis VA, Gribben JG, Freeman GJ, Nadler LM. Blockade of the CD28 co-stimulatory pathway: a means to induce tolerance. Curr Opin Immunol 1994; 6: 797807.
  • 79
    Wingren AG, Parra E, Varga M, Kalland T, Sjogren HO, Hedlund G, Dohlsten M. T cell activation pathways. B7, LFA-3, and ICAM-1 shape unique T cell profiles. Crit Rev Immunol 1995; 15: 23553.
  • 80
    Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 1992; 356: 6079.
  • 81
    Akdis CA, Joss A, Akdis M, Faith A, Blaser K. A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. Faseb J 2000; 14: 16668.
  • 82
    Joss A, Akdis M, Faith A, Blaser K, Akdis CA. IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 2000; 30: 168390.
  • 83
    Ward SG, June CH, Olive D. PI3-kinase: a pivotal pathway in T-cell activation? Immunoltoday 1996; 17: 18797.
  • 84
    Prasad KV, Cai YC, Raab M, Duckworth B, Cantley L, Shoelson SE, Rudd CE. T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif. Proc Natl Acad Sci USA 1994; 91: 28348.
  • 85
    Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol 1995; 155: 107990.
  • 86
    De Waal Malefyt R, Abrams J, Bennett B, Figdor CG, De Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes. An autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 120920.
  • 87
    Ito S, Ansari P, Sakatsume M, Dickensheets H, Vasquez N, Donnelly RP, Larner AC, Finbloom DS. Interleukin-10 inhibits expression of both interferon α and interferon γ-induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 1999; 93: 145663.
  • 88
    Mauri C, Gray D, Mushtaq N, Londei M. Prevention of athritis by interleukin 10-producing B cells. J Exp Med 2003; 197: 489501.
  • 89
    Reid CD. The biology and clinical applications of dendritic cells. Transfus Med 1998; 8: 7786.
  • 90
    Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk A. Induction of tolerance by IL-10-treated dendritic cells. J Immunol 1997; 159: 477280.
  • 91
    Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001; 2: 72531.
  • 92
    Morganti-Kossmann MC, Kossmann T, Brandes ME, Mergenhagen SE, Wahl SM. Autocrine and paracrine regulation of astrocyte function by transforming growth factor-beta. J Neuroimmunol 1992; 39: 16373.
  • 93
    Kao JY, Gong Y, Chen CM, Zheng QD, Chen JJ. Tumor-derived TGF-beta reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol 2003; 170: 380611.
  • 94
    Rivas JM, Ullrich SE. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. J Immunol 1992; 149: 386571.
  • 95
    Lidstrom C, Matthiesen L, Berg G, Sharma S, Ernerudh J, Ekerfelt C. Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood: implications for suppressor macrophages in decidua. Am J Reprod Immunol 2003; 50: 44452.
  • 96
    Kitamura M, Suto T, Yokoo T, Shimizu F, Fine LG. Transforming growth factor-beta 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells. J Immunol 1996; 156: 296471.
  • 97
    Lee K-M, Chuang E, Griffin M et al. Molecular basis of T cell inactivation by CTLA-4. Science 1998; 282: 22636.
  • 98
    Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S. Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000; 192: 30310.
  • 99
    McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, Byrne MC. CD4(+) CD25(+) immunoregulatory T cells. Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 16: 31123.
  • 100
    Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25(+) CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002; 3: 13542.
  • 101
    Nocentini G, Giunchi L, Ronchetti S, Krausz LT, Bartoli A, Moraca R, Migliorati G, Riccardi C. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci USA 1997; 94: 621621.
  • 102
    Lehmann J, Huehn J, De La Rosa M et al. Expression of the integrin alpha E beta 7 identifies unique subsets of CD25+ as well as CD25– regulatory T cells. Proc Natl Acad Sci USA 2002; 99: 130316.
  • 103
    Levings MK, Sangregorio R, Roncarolo MG. Human CD25(+) CD4(+) T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001; 193: 1295302.
  • 104
    Taylor A, Verhagen J, Akdis CA, Akdis M. T regulatory cells in allergy and health: a question of allergen specificity and balance. Int Arch Allergy Immunol 2004; 135: 7382.