Regulation of the function of CD4 T cells

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Our studies are directed at answering two basic questions concerning how immune responses are regulated: what determines whether or not an antigen, foreign or self, launches an immune response when the antigen impinges upon the immune system? Secondly, what determines, if an immune response is launched, the type of immune response, of which there are two major kinds? For example, the immune system can generate a cell-mediated response, consisting of "cytotoxic T cells", that can kill tumor cells or cells infected by a virus, and/or it can produce antibodies that, for example, neutralize toxins that some pathogenic bacteria produce. Remarkably, the immune system has a way of deciding what type of response to generate: a predominant cell-mediated response, a predominant antibody response, or a mixed response. This "decision" is often critical, as different kinds of immunity are effective against different invaders. It has become clear that a cell of the immune system, the "CD4 T helper cell", is a critical regulator of immune responses. This is in part because such T helper cells have to be activated in order for either a cell-mediated or humoral response to be generated. A central question is what circumstances determine whether antigen activates or inactivates these helper T cells? We are testing an hypothesis that tries to explain how self and foreign antigens respectively inactivate and activate their corresponding helper T cells. Such an understanding is important for making effective vaccines. The CD4 T helper cell is also critical in determining whether a cell-mediated or humoral response is induced. Cell-mediated responses involve T helper type 1, or Th1 cells, and antibody responses involve Th2 cells. When a naive CD4 T cell interacts with antigen and other cells of the immune system, resulting in its activation, details of the interactions determine whether Th1 or Th2 cells are generated. Our studies are directed at determining exactly what are the critical and different circumstances that give rise to Th1 and Th2 cells. This is again important in envisaging ways of ensuring an effective response is made against an invader.