PMID- 19572409
OWN - NLM
STAT- MEDLINE
DCOM- 20091215
LR  - 20211020
IS  - 1542-0760 (Electronic)
IS  - 1542-0752 (Print)
IS  - 1542-0752 (Linking)
VI  - 85
IP  - 10
DP  - 2009 Oct
TI  - Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters postnatal T 
      cell phenotypes and T cell function and exacerbates autoimmune lupus in 
      24-week-old SNF1 mice.
PG  - 828-36
LID - 10.1002/bdra.20603 [doi]
AB  - BACKGROUND: Untreated, more than 95% of female SWR x NZB: F(1) (SNF(1)) mice 
      spontaneously develop a fatal lupus-like glomerulonephritis by 8 months-of-age, 
      while disease onset in males is much slower. METHODS: : Timed-pregnant SNF(1) 
      mice (10 per treatment) were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin 
      (TCDD) on gestational day (GD) 12 by oral maternal gavage with 0, 40, or 80 
      microg/kg TCDD. RESULTS: Offspring of the TCDD-exposed dams showed numerous 
      alterations in T lineage cells at 24 weeks-of-age. Females but not males showed 
      decreased CD4(+)8(+) and increased CD4(-)8(-) thymocytes. Females also showed 
      increased autoreactive CD4(+)Vbeta17(a+) axillary and inguinal lymph node T 
      cells. Concanavalin A-stimulated splenocytes from prenatal TCDD-treated mice 
      produced decreased interleukin 17 (IL-17) in the females while males showed 
      increased IL-2 and IFN-gamma, and diminished IL-4. Mitogen-stimulated 
      pan-lymphoproliferative responses were significantly increased across sex by 
      TCDD. Anti-IgG and anti-C3 immune complex deposition in kidneys was present in 
      the males after TCDD, and visibly worsened in females. CONCLUSIONS: Developmental 
      TCDD exposure can permanently alter T lymphopoiesis in autoimmune-prone SNF1 
      mice. The alteration profile is beyond the classic immune suppression response, 
      to also include exacerbation and induction of a lupuslike autoimmune disease.
FAU - Mustafa, Amjad
AU  - Mustafa A
AD  - Center for Molecular Medicine and Infectious Diseases, Department of Biomedical 
      Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary 
      Medicine, Virginia Polytechnic Institute and State University Blacksburg, 
      Virginia, USA.
FAU - Holladay, Steven D
AU  - Holladay SD
FAU - Goff, Matthew
AU  - Goff M
FAU - Witonsky, Sharon
AU  - Witonsky S
FAU - Kerr, Richard
AU  - Kerr R
FAU - Weinstein, Danielle A
AU  - Weinstein DA
FAU - Karpuzoglu-Belgin, Ebru
AU  - Karpuzoglu-Belgin E
FAU - Gogal, Robert M Jr
AU  - Gogal RM Jr
LA  - eng
GR  - R21 ES013811-03/ES/NIEHS NIH HHS/United States
GR  - R21-PAR-03-121/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Birth Defects Res A Clin Mol Teratol
JT  - Birth defects research. Part A, Clinical and molecular teratology
JID - 101155107
RN  - 0 (Cytokines)
RN  - 0 (Polychlorinated Dibenzodioxins)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/immunology/*physiopathology
MH  - Body Weight/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cytokines/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Lupus Nephritis/immunology/*physiopathology
MH  - Male
MH  - Mice
MH  - Organ Size/drug effects
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - T-Lymphocytes/cytology/*drug effects/immunology
PMC - PMC2760641
MID - NIHMS138024
EDAT- 2009/07/03 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/07/03 09:00
PHST- 2009/07/03 09:00 [entrez]
PHST- 2009/07/03 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 10.1002/bdra.20603 [doi]
PST - ppublish
SO  - Birth Defects Res A Clin Mol Teratol. 2009 Oct;85(10):828-36. doi: 
      10.1002/bdra.20603.