Adrianus (Ando) van der Velden

Research Interests Continued:

A crucial step in inducing a T cell response is T cell priming; the activation, proliferation, and differentiation of naïve T cells following their initial encounter with antigen displayed on the surface of professional antigen presenting cells such as dendritic cells.  As naïve T cells proliferate and differentiate into effector T cells, they can acquire the ability to lyse infected cells or secrete cytokines that help resolve infection.

We previously showed that T cells failed to proliferate in response to antigen-laden dendritic cells when S. Typhimurium were present.  Dendritic cells are the most important professional antigen presenting cells and are a central link between the innate and adaptive immune system.  We found that S. Typhimurium killed dendritic cells, preventing presentation of antigen to T cells.  However, when we used mutant S. Typhimurium that could not kill dendritic cells, we found that the T cells remained unable to proliferate.  These results led us to conclude that while dendritic cell killing may contribute to the lack of T cell proliferation, dendritic cell killing alone was not responsible for the lack of T cell proliferation.  We further showed that, even in the absence of dendritic cells, S. Typhimurium had an inhibitory effect on T cells, blocking their proliferation.  Most recently, we showed that S. Typhimurium downmodulate expression of the T cell receptor beta chain (TCR-beta), a molecule that is essential for antigen recognition and T cell function.

Our long-term objective is to dissect the mechanism(s) by which S. Typhimurium interfere with development of T cell-mediated adaptive immunity.  Our research should provide new insight into how microbial pathogens like S. Typhimurium avoid clearance by the mammalian immune system in order to replicate within mammalian hosts.

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