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Adrianus (Ando) van der Velden

Publications

Center for Infectious Diseases

 

 

 
Adrianus Van der Velden

Assistant Professor

Ph.D., Oregon Health and Science University, 2000
240 Center for Molecular Medicine

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(631) 632-4663
(631) 632-4294

   
Research

The mammalian T cell response to Salmonella enterica serovar Typhimurium

The major focus of our research is on the role of mammalian T cells in adaptive immunity to Salmonella enterica serovar Typhimurium (S. Typhimurium), an intracellular bacterial pathogen. We use a combination of cellular and molecular approaches to determine how S. Typhimurium infection and S. Typhimurium gene expression shape and influence development of the T cell response.

Inflammatory cells of the innate immune system, such as macrophages and neutrophils, provide a first line of defense against S. Typhimurium; however, ultimate clearance of S. Typhimurium requires lymphocytes of the adaptive immune system. During infection, T cells are a key lymphocyte subset required for eliminating S. Typhimurium.

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 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. While T cells are important in adaptive immunity to S. Typhimurium, development of T cell-mediated adaptive immunity to S. Typhimurium has been described as slow and inefficient. We have been exploring why development of T cell-mediated adaptive immunity to S. Typhimurium is slow and inefficient, and whether S. Typhimurium play an active role in inhibiting development of protective immunity.

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 (TCRb), a molecule that is required for antigen recognition and T cell function.

Our long-term objective is to dissect the means 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.

Department of Molecular Genetics and Microbiology
Stony Brook University
Stony Brook, New York 11794-5222
Phone: 631-632-8800
Fax: 631-632-9797

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