During the course of an immune response, CD4+ T helper cells identify invading pathogens, proliferate, and secrete cytokines to aid in immune-mediated clearance of infection. This results in an initial expansion of effector CD4+ T cells at the peak of infection. These effector cells are divided into a number of subsets that each coordinate specialized activities as part of a pathogen-specific immune response.
As pathogen is eliminated, the number of effector CD4+ T cells is reduced to avoid potential autoimmunity. During this contraction phase, long-lived CD4+ T cells termed ‘memory’ T cells survive from the effector pool to respond more quickly and robustly to repeated encounters with the same pathogen. This effector-to-memory transition is required for the generation of both naturally occurring and vaccine-induced long-term immunity.
The importance of both effector and memory T cell populations to human health has led to intense interest in elucidating the molecular mechanisms responsible for regulating their differentiation and function. The major goal of the Oestreich laboratory’s molecular immunology research program is to understand how cell-extrinsic cytokine signals and downstream transcription factor activities are integrated to properly regulate the differentiation and function of CD4+ T helper cell populations. This work is significant, as our findings have the potential to inform more specific and selective manipulation of T cell-mediated immune responses, both advancing strategies to improve vaccine efficacy and influencing the rational design of novel immunotherapeutic approaches to treat human disease.
Active research areas within the Oestreich Laboratory Include:
- Identifying novel regulatory pathways underlying effector and memory T cell immune responses.
- Defining the role of Ikaros zinc finger transcription factors in regulating T cell differentiation and function.
- Identifying novel roles for a lymphocyte-associated transcriptional complex in promoting lymphocyte mimicry and cancer metastasis.