| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 157, Issue 6 2310-2319, Copyright © 1996 by American Association of Immunologists
ARTICLES |
NI Kerkvliet, L Baecher-Steppan, DM Shepherd, JA Oughton, BA Vorderstrasse and GK DeKrey
Department of Agricultural Chemistry, Environmental Health Sciences Center, Oregon State University, Corvallis 97331, USA.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant and prototypic ligand for the aryl hydrocarbon receptor, is a potent immunotoxicant. To understand the underlying mechanisms of TCDD immunotoxicity, we have characterized the time course of changes in CTL, alloantibody, and cytokine responses to the P815 tumor allograft in C57B1/6 mice treated with 0 or 15 microg TCDD/kg. Suppression of CTL activity by TCDD directly correlated with reduced numbers of splenic CTL effector cells identified by their CD8+CD44 high CD45RB low phenotype, while suppression of the alloantibody response correlated with a lack of expansion of the B220+ splenocyte population. Cytokine production was differentially modulated following TCDD treatment. Although type 1 cytokine production (IFN-gamma, IL-2, and TNF) was initially induced in TCDD-treated mice, production failed to increase normally after day 5. In contrast, the production of IL-1 beta, IL-4, and IL-6 was mostly unaffected by TCDD exposure. This differential effect of TCDD on cytokine production was reflected in the degree of suppression of specific alloantibody isotypes. TCDD abrogated the production of IgG2a (promoted by IFN-gamma), but had much less effect on the level of IgG1 (promoted by IL-4). IgM Ab titers were also highly suppressed. CD8+ cells were the exclusive producers of IFN-gamma and IL-2 when spleen cells from P815-injected mice were cultured in vitro on days 4 to 7 after P815 injection. However, CD4+ cells were shown to play a crucial role in the generation of both CTL and alloantibody responses, since their depletion in vivo abolished both responses. Based on similar temporal effects produced by TCDD and anti- CD4 Ab on alloimmune responses, we postulate that TCDD interferes with the initial activation of CD4+ T cells, which leads to downstream inhibition of the activation and/or differentiation of CD8+ T cells and B cells. In addition, since delayed treatment with either anti-CD4 Ab or TCDD suppressed the alloantibody but not the CTL response, TCDD may also affect later CD4+ T helper-B cell interactions.
This article has been cited by other articles:
|
|
 |
|
  T. L. Guo, R. P. Chi, D. M. Hernandez, W. Auttachoat, and J. F. Zheng Decreased 7,12-dimethylbenz[a]anthracene-induced carcinogenesis coincides with the induction of antitumor immunities in adult female B6C3F1 mice pretreated with genistein Carcinogenesis, December 1, 2007; 28(12): 2560 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Z. Shi, N. G. Faith, Y. Nakayama, M. Suresh, H. Steinberg, and C. J. Czuprynski The Aryl Hydrocarbon Receptor Is Required for Optimal Resistance to Listeria monocytogenes Infection in Mice J. Immunol., November 15, 2007; 179(10): 6952 - 6962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Lawrence, A. D. Roberts, J. J. Neumiller, J. A. Cundiff, and D. L. Woodland Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung J. Immunol., November 1, 2006; 177(9): 5819 - 5828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Vorderstrasse and B. P. Lawrence Protection against Lethal Challenge with Streptococcus pneumoniae Is Conferred by Aryl Hydrocarbon Receptor Activation but Is Not Associated with an Enhanced Inflammatory Response. Infect. Immun., October 1, 2006; 74(10): 5679 - 5686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. BOWERS, K. B. SOMMERSTED, R. T. SOWELL, G. E. BOLING, W. H. HANNEMAN, R. G. TITUS, and G. K. DEKREY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) REDUCES LEISHMANIA MAJOR BURDENS IN C57BL/6 MICE. Am J Trop Med Hyg, October 1, 2006; 75(4): 749 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Mitchell, C. A. Lockhart, G. Huang, and C. J. Elferink Sustained Aryl Hydrocarbon Receptor Activity Attenuates Liver Regeneration Mol. Pharmacol., July 1, 2006; 70(1): 163 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Funatake, N. B. Marshall, L. B. Steppan, D. V. Mourich, and N. I. Kerkvliet Cutting Edge: 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., October 1, 2005; 175(7): 4184 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Teske, A. A. Bohn, J. F. Regal, J. J. Neumiller, and B. P. Lawrence Activation of the aryl hydrocarbon receptor increases pulmonary neutrophilia and diminishes host resistance to influenza A virus Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L111 - L124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Colgan, M. Asmal, B. Yu, and J. Luban Cyclophilin A-Deficient Mice Are Resistant to Immunosuppression by Cyclosporine J. Immunol., May 15, 2005; 174(10): 6030 - 6038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ito, S.-i. Tsukumo, N. Suzuki, H. Motohashi, M. Yamamoto, Y. Fujii-Kuriyama, J. Mimura, T.-M. Lin, R. E. Peterson, C. Tohyama, et al. A Constitutively Active Arylhydrocarbon Receptor Induces Growth Inhibition of Jurkat T Cells through Changes in the Expression of Genes Related to Apoptosis and Cell Cycle Arrest J. Biol. Chem., June 11, 2004; 279(24): 25204 - 25210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Lawrence and B. A. Vorderstrasse Activation of the Aryl Hydrocarbon Receptor Diminishes the Memory Response to Homotypic Influenza Virus Infection but Does Not Impair Host Resistance Toxicol. Sci., June 1, 2004; 79(2): 304 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Inouye, T. Ito, H. Fujimaki, Y. Takahashi, T. Takemori, X. Pan, C. Tohyama, and K. Nohara Suppressive Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on the High-Affinity Antibody Response in C57BL/6 Mice Toxicol. Sci., August 1, 2003; 74(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, K.-H. Sonoda, D. E. Faunce, J. Gumperz, T. Yamamura, S. Miyake, and J. Stein-Streilein CD4+ NKT Cells, But Not Conventional CD4+ T Cells, Are Required to Generate Efferent CD8+ T Regulatory Cells Following Antigen Inoculation in an Immune-Privileged Site J. Immunol., August 1, 2003; 171(3): 1266 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Mitchell and B. P. Lawrence Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Renders Influenza Virus-Specific CD8+ T Cells Hyporesponsive to Antigen Toxicol. Sci., July 1, 2003; 74(1): 74 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Vorderstrasse, E. A. Dearstyne, and N. I. Kerkvliet Influence of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on the Antigen-Presenting Activity of Dendritic Cells Toxicol. Sci., March 1, 2003; 72(1): 103 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fujimaki, K. Nohara, T. Kobayashi, K. Suzuki, K. Eguchi-Kasai, S. Tsukumo, M. Kijima, and C. Tohyama Effect of a Single Oral Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Immune Function in Male NC/Nga Mice Toxicol. Sci., March 1, 2002; 66(1): 117 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Rier, C. L. Coe, A. M. Lemieux, D. C. Martin, R. Morris, G. W. Lucier, and G. C. Clark Increased Tumor Necrosis Factor-{{alpha}} Production by Peripheral Blood Leukocytes from TCDD-Exposed Rhesus Monkeys Toxicol. Sci., April 1, 2001; 60(2): 327 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-S. Jeon and C. Esser The Murine IL-2 Promoter Contains Distal Regulatory Elements Responsive to the Ah Receptor, a Member of the Evolutionarily Conserved bHLH-PAS Transcription Factor Family J. Immunol., December 15, 2000; 165(12): 6975 - 6983. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. W. Sulentic, M. P. Holsapple, and N. E. Kaminski Putative Link between Transcriptional Regulation of IgM Expression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin and the Aryl Hydrocarbon Receptor/Dioxin-Responsive Enhancer Signaling Pathway J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 705 - 716. [Abstract] [Full Text]
|
|
|
|
|
|
T. S. Thurmond and T. A. Gasiewicz A Single Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Produces a Time- and Dose-Dependent Alteration in the Murine Bone Marrow B-Lymphocyte Maturation Profile Toxicol. Sci., November 1, 2000; 58(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhan, A. J. Corbett, J. L. Brady, R. M. Sutherland, and A. M. Lew CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation J. Immunol., October 1, 2000; 165(7): 3612 - 3619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Shepherd, E. A. Dearstyne, and N. I. Kerkvliet The Effects of TCDD on the Activation of Ovalbumin (OVA)-Specific DO11.10 Transgenic CD4+ T cells in Adoptively Transferred Mice Toxicol. Sci., August 1, 2000; 56(2): 340 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Warren, K. A. Mitchell, and B. P. Lawrence Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Suppresses the Humoral and Cell-Mediated Immune Responses to Influenza A Virus without Affecting Cytolytic Activity in the Lung Toxicol. Sci., July 1, 2000; 56(1): 114 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Murante and T. A. Gasiewicz Hemopoietic Progenitor Cells Are Sensitive Targets of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in C57BL/6J Mice Toxicol. Sci., April 1, 2000; 54(2): 374 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Regulations and Advisories Toxicology and Industrial Health, April 1, 2000; 16(3-5): 173 - 201. [PDF]
|
|
|
|
|
|
D. M. Shepherd and N. I. Kerkvliet Disruption of CD154:CD40 Blocks Generation of Allograft Immunity Without Affecting APC Activation J. Immunol., September 1, 1999; 163(5): 2470 - 2477. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
