By Roberta Attanasio
The development of the immune system during fetal and neonatal life is negatively influenced by exposure to toxic chemicals, resulting in compromised immune function later in life. An example is fetal exposure to arsenic, which has deleterious effects on the immune response to influenza virus infection in adulthood. Now, results from a new study provide additional evidence for the role that exposure to toxic chemicals early in life plays in shaping the immune response to the influenza virus.
The study (by researchers at the University of Rochester) focused on a mouse model and the chemical 2,3,7,8-tetrachlordibenzo-p-dioxin, or TCDD for short. TCDD, a known carcinogen, is a persistent environmental contaminant usually present in a complex mixture of dioxin-like compounds. It’s a by-product of industrial processes such as pesticide and metal production, waste incineration and wood combustion, and acts via the aryl hydrocarbon receptor, which is present in all cells. The aryl hydrocarbon receptor is a ligand-activated transcription factor that controls the expression of a diverse set of genes.
The researchers designed their mouse study to expand previous epidemiological findings from human studies. These findings showed correlation between maternal exposure to pollutants that bind the aryl hydrocarbon receptor and the decreased ability of the offspring to combat respiratory infections and produce antibodies. In other words, the epidemiological findings indicated that mothers exposed to these pollutants while pregnant may give birth to babies with impaired immune function.
An effective immune response requires the coordinated action of several cell types. CD4+ T cells, one of these cell types, exist in different subsets. It has been known for several years that, by binding the aryl hydrocarbon receptor, some chemicals influence the different subsets of CD4+ T cells, thus resulting in the observed impaired immune function. However, it was not known whether or not prenatal exposure to these chemicals could cause changes in the different CD4+ T cell subsets.
The researchers that carried out the new study wanted to know whether or not fetal exposure to an aryl hydrocarbon receptor ligand (in this case TCDD) directly alters CD4+ T cell differentiation and function later in life. Thus, they exposed pregnant female mice to TCDD and then infected the adult offspring with the influenza virus. The results show that the offspring of the exposed pregnant mothers had a reduced frequency of different subsets of CD4+ T cells when compared with mice born to untreated mothers. In addition, exposed mice produced considerable lower levels of a specific class of antibodies against the influenza virus than control mice.
Then, the researchers transferred CD4+ T cells from the exposed offspring into unexposed mice. They found that, following cell transfer, the unexposed mice responded to influenza virus infection with a reduced number of CD4+ T cells specific for the virus.
CD4+ T cells play a major role in the immune response to a large variety of infectious microbes and are also involved in the development of several autoimmune diseases. Therefore, it is reasonable to speculate that exposure of the fetus to chemicals that bind the aryl hydrocarbon receptor may lead to impaired defense against several infectious microbes and to an increased risk of developing autoimmune diseases later in life.