IMMUNOLOGIST
Purpose of the Research:
One can see the immune system as an “army” of white blood cells ready to fight the invading pathogens responsible for infections.
The immune system is composed of a variety of cells that act at different layers of defense to accomplish a collection of biological processes that aim at protecting us against dangers including infections as well as tumors. Within peripheral tissues (that are exposed to the outside world: skin, lungs, gut, mucosa, etc…) there is a range of specialize phagocytic cells, including macrophages and dendritic cells. These dendritic cells act as sentinels patrolling the body to detect any pathogens as soon as they enter, regardless of the location. They trap the pathogens, such as bacteria or viruses or molecules derived from these, and migrate to sites called secondary lymphoid organs to present these molecules (called antigens) to the specific cells of the immune system; the T lymphocytes and B lymphocytes. These secondary lymphoid organs are disseminated throughout the body and can be assimilated as headquarters where the decision about the strategy that has to be developed to fight the pathogens is taken.
Different pathogens activate the dendritic cells in different ways, which in turn modifies the T and B lymphocytes responses. The dendritic cell response is part of what is termed the innate immunity, while the T and B lymphocytes make an adaptive immune response that leads to the production of specific effector CD4 T lymphocytes. Depending on the properties of the pathogens, such as its preference to stay hidden within cells intracellular pathogens or pathogens that colonize peripheral organs without entering cells extracellular pathogens, different strategies are undertaken by the immune system to fight them. There are two main strategies that are called humoral immune response or cytotoxic immune response.
My research focuses on studying how CD4 T lymphocytes that belong to the adaptive arm of the immune system get activated both in vitro and in vivo. I have always been fascinated by these CD4 T lymphocytes for they are central in shaping the type of the immune response. They act as Commandants who give orders to soldiers, including B lymphocytes and CD8 T lymphocytes, whose weapons will be directly aimed to the invading pathogens. The effector function of these soldiers depends on the type of these cells, where CD8 T lymphocytes would be the infantry soldiers that are cytotoxic and directly kill infected or tumor cells, while B lymphocytes would be the archer soldiers that produced weapons, which are termed antibodies that act at a distance.
The CD4 T cells regulate the complex workings of the overall immune response, by delivering their orders mainly through the secretion of soluble molecules that are messengers of the immunity; including interleukins (IL), growth factors, and interferons (IFN). Indeed, a naïve CD4 T cell can integrate the information carried by the dendritic cells and deliver a variety of effector functions, or messages, that are often exclusive. This led, 20 years ago, to the classification of CD4 Th cells into various categories depending on the soluble messages that they send to the various soldiers.
This highlights the adaptability and plasticity of the CD4 T cell response. In this context, it is important to identify the molecules that signal to the CD4 T lymphocytes, and understand how these molecules trigger the information inside the cell to control the induction of one type of message and not another. My projects aim at identifying new molecules that will help us understand the way CD4 T lymphocytes differentiate in vivo.
Our knowledge of the range of molecules that regulate CD4 T lymphocytes differentiation in vivo is clearly incomplete. Identifying the missing factors, and the way these factors work in combination, will be of major importance to understanding the way T cells gain the “right” effector functions and are able to establish the “right” strategy of defence against a specific pathogen. This should open up novel ways of manipulating immune responses, and may be important to the rational design of vaccines for inducing effective immunity, and also lead to the design of new therapeutic reagents that are able to modulate the immune response when such become detrimental to the host, by producing harmful effects including autoimmunity or allergic disorders.