Impact of age and sex on human CD8 T cell activation and functions

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Our immune system is composed of numerous cells and molecules that are patrolling from our blood stream to all organs. When a danger is detected in one organ these cells and molecules enter the targeted organ and start a whole cascade of events to get rid of the danger: be a potential tumor or a microbe. Amongst the white blood cells circulating in human blood, a particular cell type named CD8 T cell plays a key role in controlling microbes and abnormal cells. Following the first encounter with a threat they can recognize, CD8 T cells multiply, acquire multiple functions and then migrate into organs to find and efficiently eliminate the threat (microbes or abnormal cells). A proportion of these activated CD8 T cells remains in our body even after the threat (microbe or abnormal cell) is destroyed and stays as memory cells for extended periods of time. Accumulating evidence supports that sex and age influence CD8 T cells. Unfortunately, the factors causing such differences in women vs. men or young vs. older individuals are still incompletely understood. Notably, CD8 T cells from women can multiply more efficiently than cells from men. CD8 T cells from women exhibit greater capacity to destroy infected or abnormal cells. The differences between women and men could in part be due to sex hormones. However, CD8 T cells from post-menopause women (who have lower female sex hormones) are still more efficient than those from men of the same age. Therefore, other factors are potentially involved in these differences. The immune system becomes less efficient in older individuals compared to young adults. For example, vaccination aiming at boosting CD8 T cells to control infections such as influenza, is less efficient in older people than in young adults. As they age, individuals are exposed to multiple infections and consequently the proportion of their CD8 T cells that have been previously activated increases. The proposed research program deals with human CD8 T cells and aims to identify factors that contribute to the differences between men and women and/or between young and older adults. The factors that will be studied include soluble molecules (free-floating molecules), molecules on the surface of CD8 T cells as well as signals occurring inside these cells. In order to complete these studies various methods will be exploited from tissue culture, molecular biology and flow cytometry. Graduate students participating to this program will gain a diversified training in basic immunology, biology and complex data analysis. The final goal is to elucidate the molecular mechanisms involved in shaping CD8 T cell functions in healthy women and men across their lifespan.