Mild Maternal Smoking Deregulates Thymic T Cell Development in in Utero Cigarette Smoke-Exposed Murine Offspring

Introduction Epidemiological studies demonstrate that in utero cigarette smoke-exposure negatively affects lung development, thereby increasing risks for asthma and COPD (Svanes, Thorax 2010). Moreover, smoking in pregnancy is frequently underreported in women, where mild smoking might be concealed. Therefore, we hypothesize that mild maternal smoking could influence immune development in offspring.
Objective Is to develop a murine model of mild maternal smoking and to investigate, thereafter immune cells in thymus and lung.
Methods Female C57Bl/6 mice were exposed to mainstream cigarette smoke for 4 consecutive days prior to mating. Smoke-exposure was continued during pregnancy until birth once per day for one hour; 1 puff/min ≙ 6 cigarettes (research cigarettes 3R4F); inExpose exposure system (SCIREQ, Canada). Lung function was assessed by FlexiVent system (SCIREQ, Canada). Pulmonary and thymic T cells were analyzed by flow cytometry.
Results At PND21 (postnatal day 21), CD3+ T cells in lungs were decreased in prenatally smoke-exposed offspring with further detection of increased CD4+ T cells and decreased CD8+ T cells in both sexes. This was further investigated in the thymus, where thymic CD4+CD8-CD3- single positive (SP) T cells were increased, whereas CD4 – CD8+CD3- SP T cells were not affected in smoke-exposed offspring compared to air controls. Additionally, double-positive (CD4+CD8+) T cells were decreased in smoke-exposed offspring with a normal population of double-negative (CD4 – CD8-) T cells.
Conclusion Our data using a mild maternal smoking model revealed altered T cell composition in lung and thymus of PND21 offspring, despite normal body weight and lung function. This observation could be a first indication of disturbed T cell development in in utero smoke-exposed murine offspring with altered peripheral immune responses. This could suggest a first hint of a higher asthma susceptibility observed in prenatally cigarette smoke-exposed children. As a next step, murine thymic T cell populations of smoke-exposed offspring will be sorted and analyzed for changes at mRNA expression levels.