People

Research Interests

Work in my lab focuses on the activation and subset differentiation of CD4⁺ T lymphocytes.

• The biological consequences for individual T cells after the capture of APC membrane fragments from T-APC immunological synapse, a process termed “trogocytosis”;
• The impact of the herbicide Atrazine on the activation of CD4⁺ T cells and the mechanism underlying a significant increase in Foxp3⁺ regulatory T cells

Trogocytosis 

CD4⁺ T lymphocytes recognize antigenic peptide fragments presented on the surface of antigen presenting cells (APC) by major histocompatiblility complex (MHC) class II proteins. Triggering of the T cell antigen receptor (TCR) by binding to the MHC:peptide ligand induces dramatic morphological changes as the T cell flattens against the APC and increases contact area forming stable T-APC conjugates. This initial antigen recognition is followed by large-scale spatial and temporal molecular rearrangements of plasma membrane proteins and intracellular signaling molecules. These rearrangements lead to the formation of an ordered structure at the T-APC interface termed the immunological synapse. The synapse is involved in T cell signaling as well as the site for delivery of T cell effector functions. We have previously shown that molecules from the APC are transferred to the T cell across the immune synapse in a process called trogocytosis.

We are examining the biological significance of intercellular transfer of molecules from APC to T cells (termed trogocytosis). We have previously shown that upon dissociation from APC, T cells capture MHC:peptide molecules from the immunological synapse and imaging data suggests that these molecules continue to signal to the T cell. Our work suggests that these trogocytosed molecules sustain intracellular signaling leading to selective survival of the trogocytosis positive cells, in vitro.  We are currently investigating whether this signaling influences effector subset differentiation and effector cytokine production. Our working hypothesis is that trogocytosis contributes to control of the immune response by sustaining cell-autonomous signaling resulting in sustained effector cytokine production and skewing of CD4⁺ T cells to a T_H2-like phenotype. 

Immunotoxicology of Atrazine

We are examining the impact on Atrazine on the activation and differentiation of CD4⁺ T cells.  Atrazine is a very widely applied herbicide that the USGS  estimates contaminates 70% of the ground water in the US. It has been linked to birth defects,  cancer, immune developmental defects and  modulation of immune cell effector functions. We have shown that Atrazine inhibits lymphocyte proliferation and lymphocyte effector function.  In addition, we have shown that the frequency of Foxp3 positive regulatory T cells doubles in atrazine-treated cultures. We have recently found that male and female T cells repsonde differently to atrazine exposure.  We are now examining the impact of Atrazine-induced elevated estrogen on the induction of Tregs and Atrazine-associated inhibion of T cell activation.