Abstract
Objectives
Mucosal immunity plays a pivotal role for body defense against infection and allergy. The aim of this study was to clarify the effects of 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on mucosal immunity in the gut.
Methods
Fecal IgA level and oral tolerance induction were examined in TCDD-treated mice. Flow cytometric and histological analyses were also performed.
Results
Single oral administration of low dose 2,3,7,8-TCDD resulted in a marked decrease in IgA secretion in the gut without any effects on the cellular components of gut-associated lymphoid tissues (GALT) including Peyer’s patches (PPs) and mesenteric lymph nodes (LNs). Decressed IgA secretion by TCDD was not observed in aryl hydrocarbon receptor (AhR)-deficient mice. Flow cytometric analysis revealed that IgA B cells in PPs and the mesenteric LNs remained unchanged in the TCDD-treated mice. An immunofluorescence study also demonstrated that a significant number of cytoplasmic IgA cells were present in the lamina propria of the gut in the TCDD-treated mice. Furthermore, oral tolerance induction by ovalbumin (OVA) was impaired in the TCDD-treated mice and OVA-specific T cell proliferation occurred in the peripheral lymphoid tissues including the spleen and LNs.
Conclusions
These results suggest that a relatively low dose of TCDD impairs mucosal immunity in the gut and induces systemic sensitization by oral antigens.
Key words: TCDD, mucosal immunity, IgA, oral tolerance, allergy
Abbreviations
- OVA
ovalbumin
- PPs
Peyer’s patches
- LNs
lymph nodes
- CTL
cytotoxic T lymphocytes
- BWFI
(New Zealand Black × New Zealnad White) FI hybrid
- SLE
systemic lupus erythematosus
- HRP
horse radish peroxidase
- FITC
fluorescein isothiocyanate
- PE
phycoerythrin
- APC
allophycocyanate
- CFA
complete Freund’s adjuvant
- BSA
bovine serum albumin
- KLH
keyhole limpet hemocyanin
- TGF
transforming growth factor
- GVH
graft versus host reaction
References
- (1).Holsapple MP, Snyder NK, Wood SC, Morris DL. A review of 2,3,7,8-tetraclorodibenzo-p-dioxin-induced changes in immuno-competence. Update. Toxicology. 1991;69:219–255. [DOI] [PubMed]
- (2).Pohjanvirta R, Tuomisto J. Short-term toxicity of 2,3,7,8-tetraclorodibenzo-p-dioxin in laboratory animals: effects, mechanisms, and animal model. Pharmacol Rev. 1994;46:483–459. [PubMed]
- (3).Kerkvliet NI. Immunological effects of chlorinated dibenzo-p-dioxins. Environ Health Perspect. 1995;103:47–53 [DOI] [PMC free article] [PubMed]
- (4).Kerkvliet NI. Recent advances in understanding the mechanisms of TCDD immunotoxicity. Int Immunopharmacol. 2002; 2:277–291. [DOI] [PubMed]
- (5).Negishi T, Kato Y, Ooneda O, Mimura J, Takada T, Mochizuki H, et al. Effects of aryl hydrocarbon receptor signaling on the modulation of Th1/Th2 balance. J Immunol. 2005;175:7348–7356. [DOI] [PubMed]
- (6).Leubke RW, Copeland CB, Andrews DL. Effects of aging on resistance toTrichinella spiralis infection in rodents exposed to 2,3,7,8-tetraclorodibenzo-p-dioxin. Toxicology. 1996;136:15–26. [DOI] [PubMed]
- (7).Warren TK, Mitchel KA, Lawrence BP. Exposure to 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza A virus without affecting cytolytic activity in the lung. Toxicol Sci. 2000;56:114–123. [DOI] [PubMed]
- (8).Nohara K, Izumi H, Tamura S, Nagata R, Tohyama C. Effect of low-dose 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on influenza A virus-induced mortality in mice. Toxicology. 2002;170:131–138. [DOI] [PubMed]
- (9).Metecky J, Moro I, Underdown BJ. In: Ogara P editor. Mucosal Immunology. San Diego: Academic Press; 1993. p. 133–152.
- (10).Strobel S, Mowat A. Immune responses to dietary antigens: oral to lerance. Immuol Today. 1998;19:173–181. [DOI] [PubMed]
- (11).Faria AMC, Weiner HL. Oral tolerance: mechanisms and therapeutic applications. Adv Immunol. 1999;73:153–161. [DOI] [PubMed]
- (12).Ishikawa S, Sato T, Abe M, Nagai S, Onai N, Yoneyama H, et al. Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) in the development of murine lupus and preferential chemotaxis of B1 cells towards BLC. J Exp Med. 2001;193:1393–1402. [DOI] [PMC free article] [PubMed]
- (13).Akadegawa K, Ishikawa S, Sato T, Suzuki J, Yurino H, Kitabatake M, et al. Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for SLE. J Immunol. 2005;174:5499–5506. [DOI] [PubMed]
- (14).von Mutius E, Fritzsch C, Weiland SK, Roll G, Magnussen H. Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. Br Med J. 1992;305:1395–1399. [DOI] [PMC free article] [PubMed]
- (15).Bruce IN, Harland RW, McBride NA, MacMahon J. Trends in the prevalence of asthma and dyspnoea in first year university students, 1972–89. Quart J Med. 1993;86:425–430. [PubMed]
- (16).Schultz-Larsen F. The epidemiology of atopic dermatitis. Monogr Allergy. 1993;31:9–328. [PubMed]
- (17).Wichman HE. Possible explanation for the different trends of asthma and allergy in east and West Germany. Clin Exp Allergy. 1996;26:621–624. [DOI] [PubMed]
- (18).Hopkin JM. Mechanisms of enhanced prevalence of asthma and atopy in developing countries. Curr Opin Immunol. 1997;9:788–792. [DOI] [PubMed]
- (19).Schmidt JV, Su GH-T, Reddy JK, Simon MC. Characterization of a murine AhR null allele: Involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA. 1996;93:6731–6735. [DOI] [PMC free article] [PubMed]
- (20).Benedict JC, Lin T-M, Loeffler IK, Peterson RE, Flaws JA. Physiological role of the Aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci. 2000;56:382–388. [DOI] [PubMed]
- (21).Anderson P, Ridderstad A, McGuire J, Petterson S, Poellinger L, Hanberg A. A constitutively active aryl hydrocarbon receptor causes loss of peritoneal B1 cells. Biochem Biophys Res Commun. 2003;302:336–341. [DOI] [PubMed]
- (22).Hardy RR, Hayakawa K. Development and physiology of Ly-1 B and its human homolog, Leu-1 B. Immunol Rev. 1986;93:53–80. [DOI] [PubMed]
- (23).Kroese FGM, Ammerlaan WA, Kantor AB. Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity. Int Immunol. 1989;1:75–84. [DOI] [PubMed]
- (24).MacPherson AJ, Gatto D, Sainsbury D, Harriman GR, Hengartner H, Zinkernagel RM. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. 2000;288:2222–2226. [DOI] [PubMed]
- (25).Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nature Rev Immunol. 2003;3:331–341. [DOI] [PubMed]
- (26).Santos LMB, Al-Sabbagh A, London A, Weiner HL. Oral tolerance to myelin basic protein induces TGF-β secreting regulatory T cells in Peyer’s patches of SJL mice. Cell Immunol. 1994;157:439–444. [DOI] [PubMed]
- (27).Tsuji N, Mizumachi K, Kurisaki K. Interleukin-10-secreting Peyer’s patches are responsible for active suppression in low-dose oral to lerance. Immunology. 2001;103:458–463. [DOI] [PMC free article] [PubMed]
- (28).Spahn TW, Fontana A, Faria AMC, Slavin AJ, Eugster HP, Zhang X, et al. Induction of oral tolerance to cellular immune responses in the absence of Peyer’s patches. Eur J Immunol. 2001;31:1278–1283. [DOI] [PubMed]
- (29).Spahn TW, Weiner HL, Renner PD, Lugering N, Fontana A, Domschke W, et al. Mesenteric lymph nodes are critical for the induction of high-dose tolerance in the absence of Peyer’s patches. Eur J Immunol. 2002;32:1109–1114. [DOI] [PubMed]
- (30).Suh ED, Vistica BP, Chan C-C, Raber JM, Gery I, Nussenbiatt RB. Splenectomy abrogates the induction of oral tolerance in experimental autoimmune uveitis. Curr Eye Res. 1993;12:833–838. [DOI] [PubMed]
- (31).Yoshida H, Hachimura S, Hirahara K, Hisatsune T, Nishijima K, Shiraishi A, et al. Induction of oral tolerance in splenocyte-reconstituted SCID mice. Clin Immunol Immunopathol. 1998;87:282–291. [DOI] [PubMed]
- (32).Vinney JL, Mowat AM, O’Malley JM, Williamson E, Fanger NA. Expanding dendritic cells in vivo enhances the induction of oral tolerance. J Immunol. 1998;160:5815–5820. [PubMed]
- (33).Huag FP, Platt N, Wykes M, Major JR, Powell TJ, Jenkins CD, et al. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med. 2000;191:435–440. [DOI] [PMC free article] [PubMed]
- (34).Chirdo FG, Millington OR, Beacock-Scharp H, Mowat AM. Immunomodulatory dendritic cells in intestinal lamina propria. Eur J Immunol. 2000;35:1831–1840. [DOI] [PubMed]
- (35).Funatake CJ, Marshal NB, Stephan LB, Mourich DV, Kerkvliet NI. Activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4+CD25+ cells with characteristics of regulatory T cells. J Immunol. 2005;175:4184–4188. [DOI] [PubMed]