Elucidation of cellular targets responsible for tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of antibody responses: II. The role of the T-lymphocyte.
Various immunological assays have been applied by our laboratory in an attempt to assess the role of the T-cell in the TCDD-induced suppression of the antibody response by murine B6C3F1 splenic lymphocytes. Animals were treated in vivo (via gavage) with 1.0 microgram/kg TCDD in corn oil for 5 days before in vitro analysis of splenocyte immunocompetence and T-cell function. To study the effects on T-helper cell function, alterations in the proliferative responses of T-cells following TCDD exposure were investigated. Results show no significant difference in [3H]thymidine uptake between vehicle- and TCDD-treated whole splenocytes 24 h after in vitro stimulation with the T-cell mitogen Con A. This is consistent with the finding that IL-2 production at either 24 or 48 h after Con A stimulation of TCDD-treated lymphocytes was not significantly different from that of vehicle-treated controls. The possibility of the induction of a suppressor T-cell by TCDD was also investigated. Titration of T-cells from TCDD-treated mice into naive splenocyte cultures did not suppress the humoral response to either a T-dependent (SRBC) or a T-independent (DNP-Ficoll) antigen. In contrast, titration of cells stimulated in vitro with Con A for 48 h (a positive control for the induction of a suppressor T-cell) inhibited humoral responses of naive cells to both types of antigen. Likewise, T-cells plus macrophages from TCDD-treated mice did not suppress the in vitro humoral responsiveness of naive B-cells plus macrophages to a T-independent antigen (DNP-Ficoll). These results would indicate that an alteration in T-cell function following TCDD exposure does not play a role in the suppression of the antibody response elicited by antigen stimulation of murine B6C3F1 splenocytes.
Dooley
R K
RK
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Morris
D L
DL
Holsapple
M P
MP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D004147:Dioxins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D000072317:Polychlorinated Dibenzodioxins; D003208:Concanavalin A