ICOS and CD28: similar or separate costimulators of T cells?

The human body contains an important mechanism to protect itself against pathogens like bacteria or viruses: the immune system. T cells are central cells of the immune system and are essential in the defence against these foreign invaders. When no bacteria or viruses are around, T cell circulate in a resting state in the blood scanning the surroundings. When T cells sense the presence of unwanted guests they come into action: first they expand in numbers, by activation and cell division and then they change into cells specialised to fight the invader. The end result is a large number of T cells, armed to combat the pathogens. In the defence against foreign substances T cell signal to other cells of the immune system, so-called B cells, that invaders are present. When signalled by the T cells, these B cells start to produce'antibodies'; small substances that circulate in the blood to search and aid killing of the pathogenic substances. Production of these antibody occurs for instance when people are vaccinated. We have studied two molecules that are expressed on the surface of T cells and are mandatory for the activation, division and changing into armed T cells: CD28 and ICOS. In this thesis we have dissected the respective role of the relatively recently discovered molecule ICOS compared to the well studied molecule CD28. CD28 is mandatory for initiation of the cascade changing resting T cells into armed pool of specialized T cells. We have found that next to CD28, ICOS is also mandatory for the division and survival of T cells, resulting in expansion of the T cell pool. We looked inside the T cell and found that both molecules generate similar signals that lead to these comparable functions. Moreover, we found that both CD28 and ICOS are crucial for the antibody production after vaccination against the bacteria N. meningitidis. The similarities between ICOS and CD28 suggest that both molecules are attractive targets for immunotherapy. Activation through these molecules could boost the immune system when desirable or blocking the function could prevent aberrant T cell activation in the case of auto-immunity. Moreover, the presence of either CD28 or ICOS could be a diagnostic tool predicting the responses to vaccination.