Potential role of bacterial lipopolysaccharides in the development of autoimmune gastritis induced by neonatal thymectomy

Abstract

The role of LPS in the development of autoimmune gastritis (AIG) in BALB/c mice thymectomized on day 3 after birth (d3-Tx) was investigated in LPS-non-responder BALB/lps^d mice. The symptoms were classified into three types: (i) hypertrophic stomach (HS) and lymphocyte infiltration (LI)-double negative; (ii) HS-negative and LI-positive; and (iii) HS- and LI-double positive. The double positive type-3 was termed AIG. Following d3-Tx, LPS-responder BALB/c (Lps ⁿ) mice showed the following incidence: type-1 (14%), type-2 (14%) and type-3 (72%). In contrast, the incidence in BALB/lps^d mice was 67%, 22% and 11%, respectively. Thus the frequency of AIG development in BALB/lps^d mice was much lower than in BALB/c mice. A single administration of LPS on day 2 post-d3-Tx induced severe AIG incidence in all d3-Tx BALB/c mice but not in d3-Tx BALB/lps^d mice, suggesting that LPS influences the progression of AIG development. Formation of auto-antibodies against the proton pump (H⁺/K⁺-ATPase) seemed to be related to AIG incidence in d3-Tx BALB/c mice. In d3-Tx BALB/lps^d mice, however, higher levels of auto-antibodies were detected in the type-2 mice, whereas AIG incidence was much lower than that in d3-Tx BALB/c mice. Thus, formation of auto-antibodies against the proton pump in d3-Tx BALB/lps^d mice does not appear to correlate with AIG pathogenesis.

References

Kojima A. , Prehn RT Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 1981; 14: 15—27.

Sakaguchi S. , Fukuma K. , Kuribayashi K. , Masuda T. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 1985 ; 161: 72—87.

Fukuma K. , Sakaguchi S. , Kuribayashi K. et al. Immunologic and clinical studies on murine experimental autoimmune gastritis induced by neonatal thymectomy. Gastroenterology 1988; 94: 274—283.

De Silva HD , van Driel IR , La Gruta N. , Toh BH , Gleeson PA CD4+ T cells, but not CD8+ T cells, are required for the development of experimental autoimmune gastritis. Immunology 1998; 93: 405—408.

Smith H. , Sakamoto Y. , Kasai K. , Tung Ksk. Effector and regulatory cells in autoimmune oophoritis elicited by neonatal thymectomy. J Immunol 1991; 147: 2928—2933.

Gleesen PA , Toh BH , van Driel IR. Organ-specific autoimmunity induced by lymphopenia. Immunol Rev 1996; 149: 97—125.

Smith H. , Lou YH , Lacy P. , Tung Ksk. Tolerance mechanisms in experimental ovarian and gastric autoimmune diseases . J Immunol 1992; 149: 2212—2218.

Alderuccio F. , Toh BH , Tan SS , Gleeson PA , van Driel IR. An autoimmune disease with multiple molecular targets abrogated by the transgenic expression of a single autoantigen in the thymus. J Exp Med 1993; 178: 419—426.

Nishio A. , Hosono M. , Watanabe Y. , Sakai M. , Okumura M. , Masuda T. A conserved epitope on H+,K+-adenosine triphosphatase of parietal cells discerned by a murine gastritogenic T-cell clone. Gastroenterology 1994; 107: 1408—1414.

10.

Barrett SP , Toh BH , Alderuccio F. , van Driel IR , Gleeson PA Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia. Eur J Immunol 1995; 25: 238—244.

11.

Barrett SP , van Driel IR , Tan SS , Alderuccio F. , Toh BH , Gleeson PA Expression of a gastric autoantigen in pancreatic islets results in non-destructive insulitis after neonatal thymectomy. Eur J Immunol 1995; 25: 2686—2694.

12.

Asano M. , Tosa M. , Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of T cell subset. J Exp Med 1996; 184: 387—396.

13.

Suri-Payer E. , Kehn PJ , Cheever AW , Shevach EM Pathogenesis of post-thymectomy autoimmune gastritis-identification of anti-H/K adenosine triphosphatase-reactive T cells . J Immunol 1996; 157: 1799—1805.

14.

Scarff K. , Pettitt J. , van Driel IR , Greeson P. , Toh BH Immunization with gastric H/K ATPase induces reversible autoimmune gastritis . Immunology 1997; 92: 91-98.

15.

Suri-Payer E. , Amar A. , Thornton AZ , Shevach EM CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 1998; 160: 1212—1218.

16.

Sakaguchi S. , Sakaguchi N. , Asano M. , Itoh M. , Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor a-chains (CD 25): Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151—1164.

17.

Itoh M. , Takahashi T. , Sakaguchi N. et al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999; 162: 5317—5326.

18.

Murakami K. , Hosono M. , Maruyama H. et al. Concomitant enhancement of the response to Mls-1a antigens and the induction of post-thymectomy autoimmune gastritis in BALB/c mice. Clin Exp Immunol 1993; 92: 500—505.

19.

Silveira PA , Baxter AG , Cain WE , van Driel IR. A major linkage region on distal chromosome 4 confers susceptibility to mouse autoimmune gastritis. J Immunol 1999; 162: 5106—5111.

20.

De Silva HD , Gleeson PA , Toh BH , van Driel IR , Carbone FR Identification of a gastritogenic epitope of the H/K ATPase βsubunit. Immunology 1999; 96, 145—151.

21.

Claeys D. , Saraga E. , Rossier BC , Kraehenbuhl JP Neonatal injection of native proton pump antigens induces autoimmune gastritis in mice. Gastroenterology 1997; 113: 1136—1145.

22.

Morse SS , Sakaguchi N. , Sakaguchi S. Virus and autoimmunity: induction of autoimmune disease in mice by mouse T lymphotropic virus (MTLV) destroying CD4+ T cells. J Immunol 1999; 162: 5309—5316.

23.

Sakagami T. , Vella J. , Dixon MF et al. The endotoxin of Helicobacter pylori is a modulator of host-dependent gastritis. Infect Immun 1997; 65: 3310—3316.

24.

Katakai T. , Mori KJ , Masuda T. , Shimizu A. Differential localization of Th1 and Th2 cells in autoimmune gastritis. Int Immunol 1998; 10: 1325—1334.

25.

Nishio A. , Katakai T. , Oshima C. et al. A possible involvement of Fas-Fas ligand signaling in the pathogenesis of murine autoimmune gastritis. Gastroenterology 1996; 111: 959—967.

26.

Katakai T. , Agata Y. , Shimizu A. et al. Structure of the TCR expressed on a gastritogenic T cell clone, II-6, and frequent appearance of similar clonotypes in mice bearing autoimmune gastritis. Int Immunol 1997; 9: 1849—1855.

27.

Suri-Payer E. , Amar AZ , McHugh R. , Natarajan K. , Margulies DH , Shevach EM Post-thymectomy autoimmune gastritis: fine specificity and pathogenicity of anti-H/K ATPase reactive T cells. Eur J Immunol 1999; 29: 669—677.

28.

Claeys D. , Faller G. , Appelmelk BJ , Negrini R. , Kirchner T. The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy. Gastroenterology 1998; 115: 340—347.

29.

Bamford KB , Fan X. , Crowe SE et al. Lymphocytes in the human gastric mucosa during Helicobacter pylori infection have a T helper cell 1 phenotype. Gastroenterology 1998; 114: 482—492.

30.

D'Elios MM , Manghetti M. , De Carli M. et al. T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol 1997; 158: 962—967.

31.

Mohammadi M. , Nedrud J. , Redline R. , Lycke N. , Czinn SJ Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load . Gastroenterology 1997; 113: 1848—1857.

32.

Santucci L. , Fiorucci S. , Di Matteo F M, Morelli A. Role of tumor necrosis factor-α release and leukocyte margination in indomethacin-induced gastric injury in rats. Gastroenterology 1995; 108: 393—401.

33.

Kirkland T. , Viriyakosol S. , Perez-Perez GI , Blaser MJ Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14. Infect Immun 1997; 65: 604—608.

34.

Remick DG , Strieter RM , Eskandari MK et al. Role of tumor necrosis factor-α in lipopolysaccharide-induced pathologic alterations. Am J Pathol 1990; 136: 49—60.

35.

Pape KA , Khoruts A. , Mondino A. , Jenkins MK Inflammatory cytokines enhances the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells. J Immunol 1997; 159: 591—598.

36.

Galanos C. , Freudenberg MA , Katshinski T. , Salomao R. , Mossmann H. , Kumazawa Y. Tumor necrosis factor and host response to endotoxin. In: Morrison DC , Ryan JL. (Eds) Bacterial Endotoxic Lipopolysaccharides, Vol. II. Boca Raton: CRC Press, 1992; 75—104.

37.

Garcia-Martinez C. , Llovera M. , Lopez-Soriano FJ , del Santo B. , Angiles JM Lipopolysaccharide (LPS) increases the in vivo oxidation of branched-chain amino acids in the rat: a cytokine-mediated effect. Mol Cell Biochem 1995; 148: 9—15.

38.

Takakuwa T. , Knopf HP , Sing A. , Carsetti R. , Galanos C. , Freudenberg MA Induction of CD14 expression in Lpsn, Lpsd and tumor necrosis factor receptor-deficient mice. Eur J Immunol 1996; 26: 2686—2692.

39.

Kumazawa Y. , Kasai M. , Freudenberg MA , Mossmann H. , Coutinho A. , Galanos C. An endotoxin-hyporesponsive mouse strain of BALB/c background, BALB/lpsd. J Endotoxin Res 1996; 3 (Suppl.): 53.

40.

Morita H. , Hasunuma R. , Fujihara M. et al. Measurement of different types of endotoxin in murine plasma by pretreatment with alkaline reagent and kinetic chromogenic Limulus test . J Endotoxin Res 1997; 4: 339—346.

41.

Hongo T. , Nojima S. , Setaka M. Purification and characterization of (H+/K+)-ATPase from hog gastric mucosa . Jpn J Pharmacol 1990; 52: 295—305.

42.

Barrett SP , Gleeson PA , de Silva H. , Toh BH , van Driel IR Interferon-gamma is required during the initiation of an organ-specific autoimmune disease. Eur J Immunol 1996; 26: 1652—1655.

43.

Segal BM , Klinman DM , Shevach EM Microbial products induce autoimmune disease by an IL-12-dependent pathway . J Immunol 1997; 158: 5087—5090.

44.

Matsui K. , Yoshimoto T. , Tsutsui H. et al. Propionibacterium acnes treatment diminishes CD4+NK1.1+ T cells but induces type 1 T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells. J Immunol 1997; 159: 97—106.

45.

Takahashi M. , Ogasawara K. , Takeda K. et al. LPS induces NK1.1+ αβ T cells with potent cytotoxicity in the liver of mice via production of IL-12 from Kupffer cells. J Immunol 1996; 157: 2436—2342.

46.

Jones CM , Callaghan JM , Gleeson PA , Mori Y. , Masuda T. , Toh BH The parietal cell autoantigens recognized in neonatal thymectomy-induced murine gastritis are the alpha and beta subunits of the gastric proton pump. Gastroenterology 1991; 101: 287—294.

47.

Martinelli TM , van Driel IR , Alderuccio F. , Gleeson PA , Toh BH Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis. Gastroenterology 1996; 110: 1791—1802.

48.

Judd LM , Gleeson PA , Toh BH , van Driel IR Autoimmune gastritis results in disruption of gastric epithelial cell development . Am J Physiol 1999; 277: 209—218.