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An All Important Breakthrough Reached In Understanding T cell response For Parasitic Diseases

Sarah Craven; Alessandro Sette of the La Jolla Institute for Allergy and Immunology in San Diego, Ca.; and Susana Laucella and Miriam Postan of the Nacional de Laboratorios e Institutos de Salud in Buenos Aires, Argentina.

Chagas Disease is a tropical parasitic disease that sickens as many as 18 million people a year, mostly in the Americas, and kills 50,000 of those. The parasite that carries it, T. cruzi, is transmitted to mammals and humans through the bite of several genera of flying, biting insects. What intrigued Tarleton was that T cell response to infection from T. cruzi, while important to the body’s ability to fight disease, has remained somewhat cryptic because of the daunting complexity of the processes.

There are actually several kinds of T cells, and the ones Tarleton and his colleagues studied are the cytotoxic T cell, which scientists call CD8+. What they discovered is that the T cell response in T. cruzi is highly focused on a relatively small set of cellular features called 'epitopes,' which are part of a macromolecule that is recognized by the immune system. The specific epitopes involved are ones encoded by the trans-sialidase (or 'ts') family of genes.

'The function of the ts genes is crucial for the parasite,' said Tarleton, 'because the parasite must have sialic acids to invade cells and infect the host. But since it doesn’t have it, it must steal it from the host cells.' The problem is that T. cruzi potentially expresses more than a thousand ts genes, and this pool varies from parasite to parasite—making this set of proteins a poor choice for vaccine development, Tarleton said.

The importance of the new research, however, isn’t in specifically what happens in T. cruzi and Chagas Disease. Rather, it is a new understanding of how T cells react to infection in all parasitic diseases, including malaria, which may cause as many as 500 million infections and three million deaths annually in humans. T
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