Fewer T lymphocytes and decreased pulmonary influenza virus burden in miceexposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

The immune system is a sensitive target for the toxicity of the environment al contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD). In mice, immuno toxicity associated with exposure to TCDD includes suppression of humoral a nd cell-mediated immunity and impaired host resistance to infectious agents . However, the underlying mechanisms for these effects of TCDD are unknown. We previously reported that treatment of C57Bl/6 mice with TCDD and influe nza A virus increases mortality, impairs cytokine production, and suppresse s T cell expansion and the generation of cytotoxic T lymphocytes (CTL) in t he draining lymph node. However, the overall virus-specific cytolytic activ ity in the lung is unaffected. This enigmatic finding left several question s unanswered, including whether decreased CD8(+) lymphocytes in the lung ar e the consequence of either delayed or suppressed recruitment of cells to t he lung; whether exposure to TCDD affects the recruitment of CD4(+) cells t o the lung; and what effect TCDD treatment has on pulmonary virus burden. T o compare the kinetics of the response in vehicle- and TCDD-treated mice, w e examined the number of bronchoalveolar lavage (BAL) cells and CTL activit y in the lung through d 10 postinfection. We found that the peak day for ce llular influx and cytolytic activity in the lung is 9 d after infection. Im munophenotypic analysis of BAL cells shows that, when compared with BAL cel ls from infected controls, exposure to TCDD caused a 50% decrease in the pe rcentage and number of both CD4(+) and CD8(+) cells. When the pulmonary vir us burden was examined over time, we found that on d 1-5 postinfection, lun gs from mice exposed to TCDD generally had lower virus titers than lung hom ogenates from vehicle- treated controls. By d 9 postinfection, no influenza virus was detected in lung homogenates from either vehicle- or TCDD-treat ed mice. These findings are likely not related to the observed decrease in CD4(+) and CD8(+) BAL cells; moreover, the diminished CD4(+) population in the lung indicates that CD4(+) cells are probably not compensating for the decreased CTL generation in TCDD-treated mice. Our observation that mice ex posed to TCDD and infected with influenza virus do not have an increased pu lmonary virus burden suggests either that TCDD treatment alters the host re sponse to infection, creating a cellular environment that is less supportiv e for viral growth, or that exposure to TCDD directly affects influenza vir us, leading to impaired virus replication within lung epithelial cells.