CD4 T cells: Balancing the coming and going of autoimmune-mediated inflammation in the CNS.

The regulation of the inflammatory response is often viewed as very complex with many cellular players. The type of immune response generated is dependent upon the nature of the immune stimulation. In autoimmunity, one of the most important players is the CD4 T cell. The CD4 T cell lineage consists of a number of phenotypically and functionally distinct subsets. The unique functions of CD4 T cells are often mediated by soluble factors, which shape the nature of the immune response. In a T cell-mediated autoimmune response, such as in multiple sclerosis (MS), the CD4 T cell is thought to orchestrate and drive the immune response resulting in inflammation within the central nervous system (CNS). The extent of the inflammation must be tightly controlled or permanent tissue damage will occur. In MS, progressive debilitating disease is thought to be due to such damage. In addition to promoting inflammation, the CD4 T cell lineage also has the capacity to prevent and downmodulate inflammation. This is accomplished by specific CD4 T regulatory (Treg) cells and other regulatory feedback mechanisms. Thus although the complexity of the immune system is often viewed as too complicated for a nonimmunologist to fully understand, there are patterns that emerge that make the system clearer. One such pattern is the balance that the immune system must always maintain. A weak or slow immune response to a pathogen can lead to sickness and even death, while a too robust or uncontrolled immune response can lead to tissue damage, and for autoimmune diseases, ultimately death. How CD4 T cells maintain this balance will be discussed in the context of the CNS autoimmune disease MS.