A lymph node slice culture model to characterize T cell activation dynamics and anti-viral responses in human tissue

The development of in vitro culture methods to characterize primary T-cell responses to drugs.

Adverse drug reactions represent a major stumbling block to drug development and those with an immune etiology are the most difficult to predict. We have developed an in vitro T-cell priming culture method using peripheral blood from healthy volunteers to assess the allergenic potential of drugs. The drug metabolite nitroso sulfamethoxazole (SMX-NO) was used as a model drug allergen to establis...

Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node.

Memory T cells circulate through lymph nodes where they are poised to respond rapidly upon re-exposure to a pathogen; however, the dynamics of memory T cell, antigen-presenting cell, and pathogen interactions during recall responses are largely unknown. We used a mouse model of infection with the intracellular protozoan parasite, Toxoplasma gondii, in conjunction with two-photon microscopy, to ...

A virtual lymph node model to dissect the requirements for T-cell activation by synapses and kinapses

The initiation of T-cell responses in lymph nodes requires T cells to integrate signals delivered by dendritic cells (DCs) during long-lasting contacts (synapses) or more transient interactions (kinapses). However, it remains extremely challenging to understand how a specific sequence of contacts established by T cells ultimately dictates T-cell fate. Here, we have coupled a computational model...

Programming the lymph node microenvironment to enhance anti-tumor T cell immunity in neuroblastoma

Background and hypothesis Current cancer therapies rely on nonspecific chemotherapies which cause severe side effects without combating relapse. Therapeutic cancer vaccines aim to harness the adaptive immune response to specifically target and eliminate established tumors, while generating durable tumorspecific T cell responses to prevent relapse. Toll like receptor agonists (TLRas) such as CpG...

Melanoma-Specific T Cell Responses: and Differentiation of Human A Novel Approach to Characterize Clonality