1. Developmental TCDD Exposure and Postnatal Autoimmune Disease
SD Holladay, Anatomy and Radiology,
College of Veterinary Medicine,
University of Georgia

2. Altered selection of T cells?Cl
Altered selection of T cells?
• Targeting of thymic epithelium
(Greenlee et al. 1985; Schuurman et al. 1992)
• Altered thymic distribution of MHC class II Ag
(DeWaal et al. 1992)
• Down-regulated MHC class I gene (Q1b)
(Dong et al. 1997)
• Induced extrathymic T cell development (VTCR)
(Silverstone et al. 1994)

3. Mouse Model C57BL/6- immunologic responsive strain,
AhR high sensitivity (Ahbb phenotype).

4. Effects of perinatal exposure to TCDD on splenic T cell subsets
Spleen - C57BL/6
Effects of perinatal exposure to TCDD on splenic T cell subsets
Mean
SEM
CD4+CD8-
Male
27.31
0.80
30.58
1.11
% Expression
Female
32.85
1.04
29.26
1.80
CD4-CD8+
10.69
0.56
14.72
0.49
12.19
0.59
13.42
0.89
Vb17a TCR+
3.31
0.39
29.14
3.27
15.16
2.93
17.91
2.15
Vb3 TCR+
4.19
0.50
32.57
2.78
11.98
2.11
19.07
CD4+CD25+
0.17
2.00
0.12
2.19
0.24
2.62
0.29
0.0ug/kg
5.0ug/kg
C57BL/6
Bold = p≤0.05 student’s t test
N= 5/treatment/gender

5. ELISA dsDNA - C57BL/6 24 weeks
FEMALE
MALE *
* = p≤0.05 student’s t test
N= 5/treatment/gender

6. 0.0 µg/kg TCDD 5.0 µg/kg TCDD C57 kidney C57 kidney 0.0 µg/kg TCDD

7. Mouse Model
SNF1 ( NZB x SWR/J)- lupus nephritis-prone strain, AhR low sensitivity (Ahdd phenotype).

8. ELISA dsDNA SNF-1 24 weeks * * p ≤ 0.5, Kruskal- Wallis
FEMALE
MALE *
* p ≤ 0.5, Kruskal- Wallis
N= 5/treatment/gender

9. Kidney
SNF1 Female
Kidney
SNF1 Female
TCDD
control
Kidney
SNF1 Male
Kidney
SNF1 Male
control
TCDD