T Lymphocyte . Infection . Vaccination . Memory . Microscopy

Immune Cell Biology

CD4+ T cells are critical regulators of health and disease. Defects in T cell function can result in a variety of immune disorders including susceptibility to infection and the development of autoimmunity. Although the strength of T cell stimulation directly modulates T cell fitness and clonal dominance, how this influences the development of various effector and memory CD4+ T cell subsets is not well understood.  Using models of both infection and tolerance our lab focuses on two broad questions: (1) how does TCR signal strength regulate the quality and extent of CD4 differentiation; and (2) what are the molecular mechanisms that link TCR signal strength with the generation of diverse CD4+T cell fates?

One way that heterogeneous T cell fates can be achieved is through asymmetric cell division which results in two daughter cells with distinct differentiation properties.  Alternatively, T cell heterogeneity might be a result of stochastic interclonal diversification, in which differential T cell priming or reencounter with antigen dictates the probability and extent of further T cell differentiation.  Using continuous time-lapse microscopy, we are able to monitor the temporal expression of surface markers and transcription factors expressed by single T cells cultured under distinct differentiation conditions.  By reconstructing the phenotypic and proliferative history of divergent T cell family trees, we aim to define and uncover novel molecular pathways underlying T cell fate decisions.

For more information, please visit the Immune Cell Biology Lab website.