Abstract
Allergic eosinophilic gastroenteritis is characterized by elevated total IgE, specific IgE to food antigens, and eosinophilia of tissue and blood. Because the lymphokines IL-4, IL-5, and γ-interferon, regulate IgE synthesis, and eosinophilopoiesisin vitro, we examined whether there is an imbalance in their production in allergic eosinophilic gastroenteritis. To explore this hypothesis, three adult patients with allergic eosinophilic gastroenteritis were studied. Flow cytometric studies of peripheral blood mononuclear cells from these patients did not reveal evidence of T cell activation or disturbance of T cell numbers or subsets. T cells were capable of normal mitogenic activationin vitro. IL-4 and IL-5 production were markedly elevated with mitogenic stimulation. Most IL-4 and IL-5 production was by CD4+ T cells. Synthesis of IL-5 by CD4+ T lymphocytes in three patients and CD8+ T lymphocytes in two patients occurred in the absence of mitogen. Mitogen-stimulated GM-CSF and γ-interferon synthesis by CD4+ T cells was normal. Lymphokine mRNA in total cellular RNA derived from endoscopic biopsies was examined by reverse transcription/polymerase chain reaction. Mucosal biopsies from control subjects and most biopsies from allergic eosinophilic gastroenteritis patients contained less than 10−8 μg IL-5 mRNA/1 μg total cellular mRNA. γ-Interferon mRNA was not detected by reverse transcription/ polymerase chain reaction in biopsies from patients with allergic eosinophilic gastroenteritis but was present in controls. These lymphokine abnormalities are consistent with the elevated IgE and eosinophilia seen in allergic eosinophilic gastroenteritis and suggest that strategies targeting T lymphocytes may be efficacious in treatment of this disease.
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References
Min K-U, Metcalfe DD: Eosinophilic gastroenteritis.In Immunology and Allergy Clinics of North America, Vol 11, JA Anderson (ed). Philadelphia, W. B. Saunders, 1991, pp 799–813
Scudamore HH, Phillips SF, Svedlund HA, Gleich GJ: Food allergy manifested by eosinophilia, elevated immunoglobulin E level, and protein losing enteropathy: The syndrome of allergic gastropathy. J Allergy Clin Immunol 70:129–138, 1982
Snapper CM, Paul WE: Interferon-γ and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236:944–947, 1987
Finkelman FD, Holmes J: Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303–333, 1990
Thyphronitis G, Tsokos GC, June CH, Levine AD, Finkelman FD: IgE secretion by Epstein Barr virus-infected purified human B lymphocytes is stimulated by IL-4 and suppressed by interferon-γ. Proc Natl Acad Sci USA 86:5580–5584, 1989
Campbell HD, Tucker WQJ, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ, Sanderson CJ, Young IG: Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci USA 84:6629, 1987
Motoji T, Okada M, Takanashi M, Masada M, Takana K, Oshimi K, Misoguichi H: Induction of eosinophilic colonies by interleukin-5 on acute myeloblastic leukemia cells. Br J Hematol 74(2):169–172, 1990
Wang JM, Rambaldi A, Biondi A, Chen ZG, Sanderson CJ, Mantovani A: Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol 19:701–705, 1989
Yamaguchi Y, Hayashi Y, Sugama Y, Miura Y, Kasshara T, Kitamura S, Torisu M, Mita S, Tominaga A, Takatsu K, Suda T: Highly purified murine interleukin 5 stimulates eosinophil function and prolongs in vitro survival. J Exp Med 167:1737–1742, 1988
Fujisawa T, Abu-Ghazaleh R, Kita H, Sanderson CJ, Gleich GJ: Regulatory effects of cytokines on eosinophil degranulation. J Immunol 144:642–646, 1989
Owen WF, Rothenberg ME, Petersen J, Weller PF, Silberstein D, Sheffer AL, Stevens RL, Soberman RJ, Austen KF: Interleukin 5 and phenotypically altered eosinophils in the blood of patients with the hypereosinophilic syndrome. J Exp Med 170:343–348, 1989
Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA: Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 167:219–224, 1988
Walsh GM, Hartnell A, Wardlaw AJ, Kurihara K, Sanderson CJ, Kay AB: IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in leucocyte integrin (CD11/18)-dependent manner. Immunology 71(2):258–265, 1990
Pene J, Chretien I, Rousset F, Briere F, Bonnefoy JY, de Vries JE: Modulation of IL-4 induced human IgE production in vitro by IFN-γ and IL-5: The role of soluble CD23. J Cell Biochem 39:253–264, 1989
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest Suppl 21:77–89, 1968
Weiner MS, Biano C, Nussenzweig V: Enhanced binding of neuraminidase treated sheep erythrocytes to human T lymphocytes. Blood 42:939–946, 1973
Indiveri F, Huddlestone J, Pellegrino MA, Ferrone S: Isolation of human T lymphocytes: Comparison between wool filtration and rosetting with neuraminidase (VCN) and 2-aminoethylisothiouronium bromide (AET)-treated sheep red blood cells. J Immunol Methods 34:107–115, 1980
Horgan KI, van Seventer GA, Shimizu Y, Shaw S: Hyporesponsiveness of “naive” (CD45RA+) human T cells to multiple receptor mediated stimuli but augmentation of responses by co-stimuli. Eur J Immunol 20:1111–1118, 1990
Limaye AP, Abrams JS, Silver JE, Ottesen EA, Nutman TB: Regulation of parasite induced eosinophilia: Selectively increased interleukin 5 production in helminth-infected patients. J Exp Med 172:399–402, 1990
Freedman DO, Lujan-Trangay A, Steel C, Gonzalez-Peralta C, Nutman TB: Immunoregulation in onchocerciasis. Functional and phenotypic abnormalities of lymphocyte subsets and changes with therapy. J Clin Invest 88:231, 1991
Chomczynski P, Sacchi N: Single step method of RNA isolation by acid guanidinum thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987
Sambrook J, Fritsch EF, Maniatis T: In vitro amplification of DNA by the polymerase chain reaction.In Molecular Cloning. A Laboratory Manual. New York, Cold Spring Harbor Laboratory Press, 1989, pp 14.2–14.35
Cebrian M, Cerrara AD, DeLandazuri MD, Acevedo A: Three different antigen specificities within the leukocyte common antigen or T200 complex: A biochemical cell distribution, and functional comparative study.In Leukocyte Typing III, AJ McMichael,et al. (eds). Oxford, Oxford University Press, 1987, pp 225–227
Terry LA, Brown MH, Beverly PCL: The monoclonal antibody, UCHL-1 recognizes a 180,000 MW component of the human leukocyte common antigen, CD45. Immunology 64:331–336, 1988
Zeitz M, Schieferdecker HL, Ullrich R, Jahn H-V, James SP, Riecken EO: Phenotype and function of lamina propria T lymphocytes. Immunol Res 10:199–206, 1991
Sarnaki S, Begue B, Jarry A, Cerf-Bensussan N: Human intestinal intraepithelial lymphocytes, a distinct population of activated T cells. Immunol Res 10:302–305, 1991
Ishii Y, Takami T, Yuasa H, Takei T, Kikuchi K: Two distinct antigen systems in human B lymphocytes: Identification of cell surface and intracellular antigens using monoclonal antibodies. Clin Exp Immunol 58:183–192, 1984
Norton AJ, Isaacson PG: Monoclonal antibody L26: An antibody that is reactive with normal and neoplastic B lymphocytes in routinely fixed and paraffin was embedded tissue. J Clin Pathol 40:1405–1412, 1987
Mason DY, Comans-Bitter WM, Cordell JL, Verhoeven MAJ, van Dongen JJM: Antibody L26 recognizes an intracellular epitope on the B-cell-associated CD20 antigen. Am J Pathol 136:1215–1222, 1990
Crabtree GR: Contingent genetic regulatory events in T lymphocyte activation. Science 243:355–361, 1989
Jaffe JS, Mullin GE, Braun-Elwert L, Metcalfe DD, James SP: IL-5 RNA production in gastric mucosa in eosinophilic gastroenteritis. J Allergy Clin Immunol 87:349, 1991 (abstr)
Waksman BH, Ozer H: Specialized elements in the immune system. Prog Allergy 21:1–113, 1976
King CL, Nutman TB: Regulation of the immune response in lymphatic filariasis and onchocerciasis. Immunol Today 12(3):A54-A58, 1991
van Haelst Pisani C, Kovach JS, Kita H, Leiferman KM, Gleich GJ, Silver JE, Denin R, Abrams JS: Administration of interleukin-2 results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer. Blood 78(6): 1538–1544, 1991
Bohjanen PR, Okajima M, Hodes RJ: Differential regulation of interleukin 4 and interleukin 5 gene expression: A comparison of T cell gene induction by anti-CD3 or by exogenous lymphokines. Proc Natl Acad Sci USA 87:5283–5287, 1990
Parronchi P, Macchia D, Piccini MP, Biswas P, Simonelli C, Maggi E, Ricci M, Ansari AA, Romagni S: Allergen and bacterial antigen specific T cell clones established from atopic donor show a different profile of cytokine production. Proc Natl Acad Sci USA 88(10):4538–4542, 1991
Smith CL, Moller G, Severinsen E, Hammarstrom L: Frequencies of interleukin-5 mRNA-produting cells in healthy individuals and in immunoglobulin-deficient patients, measured by in situ hybridization. Clin Exp Immunol 81(3):417–422, 1990
Enokihara H, Furusawa S, Nakakubo H, Kajitani H, et al: T cells from eosinophilic patients produce interleukin-5 with interleukin-2 stimulation. Blood 73(7):1809–1813, 1989
Gascan H, Gauchat JF, Aversa G, Van Vlassclaer P, de Vries JE: Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signalling pathways. J Immunol 147(1):8–13, 1991
Zhang K, Clark EA, Saxon A: CD40 stimulation provides and IFN-gamma-independent and IL-4-dependent differentiation signal directly to human B cells for IgE production. J Immunol 146(6):1836–1842, 1991
Field EH, Noelle RJ, Rouse T, Goeken K, Waldschmidt T: Evidence for excessive Th2 CD4+ subset activity in vivo. J Immunol 151(1):48–59, 1993
Yamamoto M, Fujihashi K, Beagley KW, McGhee JR, Kiyono H: Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of the cell cycle produce IFN-gamma and IL-5. J Immunol 150(1):106–114, 1993
Maggi E, Parronchi P, Manetti R, Simonelli C, Piccini MP, Rugiu FS, DeCarli M, Ricci M, Romangnani S: Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol 148(1):2142–2147, 1992
Bury TB, Radermecker MF: Depression of polymorphonuclear chemotaxis and T-lymphocyte proliferation following histamine inhalation in man. Eur Resp J 2(9):828–833, 1989
Meretey K, Chien HD, Falus A, Walcz E: Effect of histamine on T cell colony formation of PHA-stimulated cells. Agents Actions 27(1–2):215–217 1989
Miller AM, Elfenbien GJ, Barth KC: Regulation of T-lymphopoiesis by arachidonic acid metabolites. Exp Hematol 17(2):198–202, 1989
Vivier E, Deryckz S, Wang JL, Valentin H, Peronne C, de Vries JE, Bernard A, Benveniste J, Thomas Y: Immunoregulatory function of paf-acether. VI. Inhibition of T cell activation via CD3 and potentiation of T cell activation via CD2. Int Immunol 2(6):545–553, 1990
Behrens TW, Goodwin JS: Control of human T cell proliferation by platelet-activating factor. Int J Immunopharmacol 12(2): 175–184, 1990
Orlov SM, Vlasov AA, Pipatkina L, Dergovsov AA, Kulikov VI: Mechanism of suppression of human peripheral blood lymphocyte proliferation by platelet activating factor. Biul Eksp Biol Med 108(7):69–71, 1989
de Waal Malefyt R, Abrams J, Bennet B, Figdor CG, de Vries JE: Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory of IL-10 produced by monocytes. J Exp Med 174:1209–1220, 1991
Braun-Elwert L, Mullin GE, James SP: Lymphokine mRNA transcripts in the normal human intestinal mucosa (submitted for publication)
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Jaffe, J.S., James, S.P., Mullins, G.E. et al. Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and γ-interferon (γ-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis. J Clin Immunol 14, 299–309 (1994). https://doi.org/10.1007/BF01540983
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DOI: https://doi.org/10.1007/BF01540983