Phenotypic analysis of spleen, thymus, and peripheral blood cells in aged C57B1/6 mice following long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
A mouse model was used to identify potential biomarkers of exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Female C57B1/6 mice were treated weekly with 0.2 microgram TCDD/kg body weight or vehicle for 14-15 months. Phenotypic analysis by flow cytometry identified the major cell subpopulations in the spleen, thymus, and peripheral blood as defined by the expression of CD4, CD8, B220, and Mac-1 molecules. These subpopulations were further characterized for the expression of I-A, Pgp-1, CD45RB, and/or T cell receptor antigens (CD3, alpha beta, gamma delta). A group of young (4 months old) mice was evaluated concurrently to document immunophenotype alterations associated with aging. Results showed several age-related changes in phenotype distribution in the spleen and blood, but not in the thymus, despite significant age-dependent thymic involution. The age-dependent changes in splenic phenotypes included a decreased frequency of CD4+ cells and a major shift in the frequency distribution from naive T cells to effector and memory T cells as defined by Pgp-1 and CD45RB expression. These phenotypic changes in the spleen due to aging correlated with similar changes in the blood, providing preliminary support for the use of spleen cells as surrogates for blood in the development of biomarkers of immunotoxicity. In comparison to the effects of aging, TCDD treatment produced relatively subtle changes in immunophenotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
Oughton
J A
JA
Department of Agricultural Chemistry, College of Veterinary Medicine, Oregon State University, Corvallis 97331, USA.
Pereira
C B
CB
DeKrey
G K
GK
Collier
J M
JM
Frank
A A
AA
Kerkvliet
N I
NI
D000375:Aging; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000276:immunology / Q000633:toxicity*; D011946:Receptors, Antigen / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D000072317:Polychlorinated Dibenzodioxins; D011946:Receptors, Antigen