How does the receptor shape the immune response

Immune cells are specialized to ensure the most effective defense against viruses and other pathogens. Researchers at the University of Basel shed light on this specialization in T cells and showed that it occurs differently in the context of acute and chronic infection. This may be appropriate for new approaches against chronic viral infections.

Researchers led by Professor Caroline King from the University of Basel have developed a method for studying T-cell specialization in the context of infection. In the magazine eLife, They report on the different directions this specialty is taking, depending on whether it occurs in the context of an acute viral infection such as influenza or a chronic infection such as HIV infection or malaria, which the body can no longer cope with.

The study focused on so-called helper T cells. When such a cell is activated by a viral infection, it can specialize in one of two ways: into a Th1 cell, which drives a highly inflammatory killer T cell response, or into a T-cell helper cell (Tfh), which primarily supports antibody production. So the balance between Th1 and Tfh cells has important implications for the extent of inflammation in the body’s immune response.

However, there are still gaps in our knowledge of how the T helper cell determines exactly which path to take when specializing. One factor that may play an important role is how robust the T helper cell activation – or more precisely, the receptor for T cells. A T cell receptor is a type of molecular sensor found on the cell surface that is more or less identical to a portion of the pathogen. The better they match, the more activate the receptor is.

To date, however, it has not been possible to study the role of T-cell receptor signaling strength in the context of viral infection because researchers lack a suitable experimental model. King and her team have now managed to develop one (see box) in collaboration with Professor Daniel Pinchwer’s research group, such as King in the Department of Biomedicine.

The results of their analysis surprised the researchers: T-cell receptor activation plays a role, but the opposite, depending on whether the infection is acute or chronic. Strong activation resulted in more inflammatory Th1 cells in acute viral infection. However, in chronic infections, vigorous activation results in more non-inflammatory Tfh cells.

“The reason behind this may be the evolutionary adaptation of nature to protect her body,” explains Dr. Marco Kunzley, first author of the study. “If too many inflammatory Th1 cells are produced for too long during a chronic infection, it will cause long-term damage to the body’s organs.”

The experiments also yielded another interesting finding: Th1 cells that form as a result of impaired activation can continue to function longer in chronic infection than if their specialization was due to vigorous activation of the receptor. This is important because Th1 cells “tire” over time in chronic infections.

King summarizes the significance of the findings: “Our results add a piece to the T-cell depletion puzzle and may contribute – as a first step – to new approaches to treating chronic viral infections.”

Context box: Measurement of T cell fate

For their new method, the research group relied on mice with helper T cells that all carry the same receptors, and which recognize a specific virus (chorioamnionitis lymphocytic virus or LCMV). The researchers specifically mutated this LCMV to aggressively activate the T-cell receptor, only at a moderate or weak level. Additionally, there are two minimal variants of LCMV, one that leads to acute infection and the other to chronic infection. Thus, researchers were able to infect mice with various virus variants and study the further development of T cells in their blood – on the one hand in the context of an acute condition, on the other hand in the context of a chronic virus. infection.


https: //www.Unipas.the classroom /at/News and Events /News /Uni-Research /How the receptors shape the immune response.programming language
http: // dx.Resonate.Deer /10.7554 /eLife.61869

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