A major goal is to understand the mechanisms of T cell exhaustion during chronic infections. Prior work studying CD8 T cell responses during chronic viral infections has demonstrated that virus-specific CD8 T cells often lose effector functions and fail to acquire key memory T cell properties such as homeostatic proliferation (i.e. become exhausted). Using a variety of approaches including multiparameter flow cytometry, systems biology and global gene expression profiling and genetically modified mice we are defining cellular and transcriptional pathways involved in T cell exhaustion and normal memory T cell differentiation.
Some of areas of considerable current interest include inhibitory receptors (e.g. PD-1, LAG-3), transcription factors and inflammatory pathways. In addition, we are examining how co-infection with two pathogens can impact T cell memory.
Others are investigating the mechanisms of T cell mediated protective immunity to influenza virus, enteric viral infection and age-related changes in T cell immunity in both mice and humans.