PMID- 10413190
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 134
IP  - 1
DP  - 1999 May 3
TI  - Persistent suppression of delayed-type hypersensitivity in adult F344 rats after 
      perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
PG  - 79-88
AB  - Recently we observed a suppressed delayed-type hypersensitivity (DTH) response to 
      bovine serum albumin (BSA) in the 4-5-month-old offspring of F344 rat dams 
      receiving as little as 1.0 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg 
      on gestational day (GD) 14. This study was designed to characterize better this 
      suppression of the DTH response. First, the persistence of the DTH suppression 
      was determined by measuring the DTH response to BSA in the offspring of dams 
      dosed orally with 3.0 microg TCDD/kg on GD14 as well as in age-matched controls 
      at 4, 8, 12 and 19 months of age. TCDD significantly suppressed the males' DTH 
      response through 19 months of age. While the females' DTH response was reduced at 
      8, 12 and 19 months, significant suppression was observed only at 4 months of 
      age. Secondly, the lowest maternal dose of TCDD that produced DTH suppression was 
      determined by measuring the DTH response to BSA in the 4- and 14-month-old 
      offspring of dams dosed orally with 0, 0.1, 0.3 or 1.0 microg TCDD/kg on GD14. In 
      the males, suppression was observed at a maternal dose as low as 0.1 microg 
      TCDD/kg at 14 months of age, while a maternal dose of 0.3 microg TCDD/kg was 
      necessary to cause suppression in the 14-month-old females. Both males and 
      females were more sensitive to the suppression at 14 months of age than at 4 
      months of age. Lastly, the DTH response to a second antigen was examined by 
      measuring the DTH response to either BSA or keyhole limpet hemocyanin (KLH) in 
      the 5- or 4-month-old male offspring, respectively, of dams dosed orally with 
      either 0 or 3.0 microg TCDD/kg on GD14. The DTH response to both antigens was 
      suppressed significantly. Phenotypic analysis was performed on thymus and lymph 
      node suspensions. Significant effects in the thymus included an increased 
      percentage of gammadelta TCR+ cells and a decreased percentage of gammadelta 
      TCR+/CD4- CD8- and MHCI- MHCII- cells. In the popliteal lymph node draining the 
      BSA-injected footpad, there was a decreased percentage of gammadelta TCR+ and 
      MHCI- MHCII- cells and an increased percentage of MHCI+ cells. In conclusion, the 
      suppression of the DTH response associated with perinatal TCDD exposure is 
      persistent through late adulthood, occurs at a low dose (i.e. 0.1 microg TCDD/kg) 
      to the dam, and is more pronounced in males than females. While phenotypic 
      analysis identified differences in subsets of thymocytes and lymph node cells 
      between control and TCDD exposed offspring, no clear correlations were 
      established between altered subpopulations and suppressed DTH responses.
FAU - Gehrs, B C
AU  - Gehrs BC
AD  - Curriculum in Toxicology, University of North Carolina at Chapel Hill, 27599, 
      USA.
FAU - Smialowicz, R J
AU  - Smialowicz RJ
LA  - eng
GR  - 5 T32 ES07126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetus/*drug effects
MH  - Histocompatibility Antigens Class I/analysis
MH  - Histocompatibility Antigens Class II/analysis
MH  - Hypersensitivity, Delayed/*prevention & control
MH  - Male
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Antigen, T-Cell, gamma-delta/analysis
MH  - T-Lymphocyte Subsets/drug effects
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - S0300-483X(99)00024-4 [pii]
AID - 10.1016/s0300-483x(99)00024-4 [doi]
PST - ppublish
SO  - Toxicology. 1999 May 3;134(1):79-88. doi: 10.1016/s0300-483x(99)00024-4.