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Secrets of immune response illuminated in new study
Date:2/9/2012

ls survive in the host in an inactive state, "remembering" the cognate antigen to which they are related. Should they re-encounter this antigen, they can speedily mount a response, liberating IFN-λ.

An understanding of how IFN-λ release is regulated and the complex pathways involved in the production of this key cytokine remains incomplete. The current study demonstrates that the release of IFN-λ by memory T cells can also occur without the activation of these cells by direct contact with the disease antigen. In this way, memory CD8+ T cells also contribute to the host's innate immune response.

The mechanism for this antigen-independent immune response is the focus of the current study. The team's results significantly advance the understanding of such pathways and their subtle regulation, and may stimulate new biomedical approaches to interfering with and disabling disease-causing intruders.

In the new study, the group found that the antigen-independent production of IFN-λ by memory T cells relies on another cell type, known as splenic dendritic cells. Such cells contain so-called NOD-like receptors (NLRs). The NLR's are able to sniff out pathogen-associated molecular patterns. When they sense these distinctive patterns, the NLRs sound the alert.

While their more familiar cousins, the TOLL-like receptors, sense pathogen-associated molecular patterns in the extracellular space, NLRs sense pathogenic traces in the intracellular compartments. Further, once NLR's have successfully detected their target, they assemble large protein complexes in the dendritic cell, known as inflammasomes.

In the case of bacterial invasion, the NLR inside the splenic dendritic cell is triggered when it senses flagellina protein associated with bacterial flagellum. The NLR then assembles the inflammasome complex, which produces two key pro-inflammatory interleukinsIL-1 and IL-18. It is the second of these that will migrate f
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Contact: Joseph Caspermeyer
Joseph.Caspermeyer@asu.edu
Arizona State University
Source:Eurekalert  

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