Differentiation of Regulatory T Lymphocytes
The mTOR Protein Kinase Is a Key Mediator of the CD4 T Cells
Jun 21, 2009
A lymphocyte is a type of small white blood cell that carries out the important function of the immune system. The immune system is the mammalian system that defends the body against invading microbes. There are two main categories of lymphocytes, the large granular lymphocytes and the small lymphocytes. The large granular lymphocytes are commonly known as the natural killer cells (or NK cells). The small lymphocytes are the T cells and B cells. Both T and B cells recognize specific antigens.
T Lymphocytes
Among T cells there are several subsets of cells with very different and specialized functions. The two main subsets of T cells are known as CD4 and CD8 cells. CD4 and CD8 are proteins expressed at the surface of lymphocytes and also help to identify the two subsets of T cells. CD4 cells are called helper T cells, which help other cells of the immune system by promoting their activation. CD8 T cells, or cytotoxic T cells, directly attack infected or malignant body cells.
CD4 Lymphocytes and T regulatory cells
Among CD4 T helper cells, is a particular subclass known as suppressor or regulatory T cells. These cells are vital for the maintenance of immunological tolerance. Instead of helping the activation of immune cells, they decrease their activation, and lead the immune response toward a terminal stage. T regulatory cells also have the role of suppressing auto-reactive T cells that may attack body cells during an autoimmune reaction. Two major classes of CD4 T regulatory cells have been reported. The natural T reg naturally arises from the thymus, while the induced T reg cells occur by activation during the immune response.
The balance between regulatory T cells and effector T cells has an important role to play not only during the immune response but also in controlling human disease. For example T regulatory cells in cancer tissue could decrease the immune response against the tumor cells and favor the development of a tumor. This hypothesis is supported by the fact that a high number of regulatory T cells in cancerous tissues is often associated with a poor outcome for patients. Regulatory T cells have recently attracted the interest of scientists in the area of anti-tumoral strategy.
Molecular Mechanisms of CD4 Regulatory Cells Differentiation
A recent study, published by Jonathan D Powell and colleagues in the prestigious scientific journal Immunity, describes an important molecular mechanism regulating the development of the CD4 induced T regulatory cells. The studied is entitled "The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment" (Immunity, vol 832, pp 832-844, June 2009).
In their study, the scientists from John Hopkins University School of Medicine (Baltimore, USA), use genetically modified mice that lack the mTOR protein in the T cells. These T cells are unable to differentiate in T helper cells. Instead they differentiate in regulatory CD4 T cells with the suppressive activity that characterizes them.
Since regulatory CD4 cells may influence the outcome of human disease, this study opens new avenues in the pharmacological approaches to regulate immune tolerance in auto-immune disease or cancer.
