T Cell-mediated Rejection: Emerging Relationships — Puzzles and Paradoxes

12:40: The Intertwined Relationships between Alloimmunity and Protective Immunity

Aneesh K. Mehta, Emory University, Atlanta, USA

Successful organ transplantation requires effective suppression of undesired T cell-dependent rejection without inhibition of protective immunity against pathogens. Memory T cells make up almost 50% of the adult T cell compartment and are poised for rapid recall response to their cognate antigens, usually derived during previous pathogen exposures. However, this protective immune memory can serve as a barrier to immunologic acceptance of an allograft. Pathogen-specific immune memory may be degenerative and cross-react with potential allo-antigens, a process known as heterologous immunity. These cross-reactive memory subsets may be more resistant, in fact, to newer immunosuppressive strategies, such as depletive antibodies and co-stimulation blockade. More recent data suggest that there may exist specific subsets of immunologic memory that are more alloreactive than others. The use of multi-target immunosuppressive regimens has allowed us to control alloimmunity more efficiently. However, one of the major ramifications of these advancements is the creation of unique holes in protective immunity, leading to rare infectious diseases becoming more common in the realm of transplantation. The progression of these deleterious post-transplant processes seems to be patient-, pathogen-, and immunosuppressive regimen specific. This lecture will discuss ongoing research into the specific mechanisms leading to heterologous immunity, its influence on allo-specific immunologic responses, and its implications for the development of tailored immunosuppressive regimens.