1. Costimulation-mediated Subset Conversion of CD4+ T Lymphocytes.
Dec.2(WED), 11:00 / Auditorium (1F), PBC
Byoung S. Kwon
Eutilex and Tulane University
The first interaction between T lymphocyte and dendritic cell (DC) is one of the most important events in shaping the adaptive immunity. T cells receive not only antigenic information through TCR but also accessory signals through costimulatory receptors when T cells encounter DC which carries antigenic peptides in a lymph node. A number of costimulatory receptors/ligands are known and grouped into Ig and TNFR supergene families. They control the level of adaptive immune responses; most of them produce signals to promote immune responses but some counteract such activities. Expression of some members are induced strictly upon antigenic stimulation and have a single ligand, while others express broadly and have many different partners to interact. The costimulatory receptors/ligands have become targets for immunotherapy. Under the hypothesis that T cell activation requires intermediary steps, we isolated molecules that were induced when a T cell receptor engaged with a specific antigen. This led to the discovery of the 4-1BB(CD137)-4-1BBL(CD137L), and AITR(CD357)-AITRL(CD357L) systems. These molecules are induced on T cells and antigen-presenting cells when T cells bind specific antigens. This property has been used to enhance or suppress immune responses in an antigen-specific fashion. We have shown that the 4-1BB system is useful for treating cancers as well as autoimmune diseases. Modulation of AITR leads to conversion of CD4+ T cell phenotypes, and even regulatory T cells can be converted to IFN-gamma-producing effector cells. The immune modulatory activities of the AITR-AITRL system have been found to be powerful tool for cancer immunotherapy because regulatory T cells are major huddle in cancer therapy. My presentation will focus on the biology of AITR and its role in subset conversion of human CD4+ T lymphocytes.
Inquiry: Prof. Charles Surh (Tel ) or AIM Administrative Team (Tel ,