Immune System: Lymph Nodes with Location Memory

Photo: Cells

A regulatory T cell (blue) in electronmicroscopic magnification, interacting with bacteria cells (green); © HZI/Rohde

Regulatory T cells (or Tregs for short) guide all of the other immune cells. How Tregs become Tregs in the first place has been only incompletely understood – until now. Scientists have recently gleaned important new insights into the workings of these cells.

As it turns out, origin is key – greater numbers of Tregs are produced within certain lymph nodes than in others. Without regulatory T cells, the human defence system would not work properly. Defender cells would be fiercely fighting off even harmless foreign substances like the parts of certain kinds of food, for example, as the immune system would simply not be tolerant towards these harmless substances. This tolerance is mediated through the Tregs – they are tolerogenic.

They instruct other immune cells as to which intruders really do need to be fought off and which ones do not pose a threat. However, even regulatory T cells have to first acquire this unique skill. What we have known for some time now is that they receive their training inside lymph nodes. “Lymph nodes are basically the immune system’s meeting points if you will,” says Prof. Jochen Hühn of the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany. “Here, different types of immune cells meet up and also encounter antigen.” An antigen is a structure the immune system is able to recognize like component parts of pathogens or foods.

The researchers compared the development of murine T cells obtained from lymph nodes from various locations in the body, like the liver, intestine, and skin. In the process, they learned that more Tregs capable of teaching other cells to be tolerant of food antigens are made inside lymph nodes of the liver and intestine – a property the lymph nodes maintained even when they were transplanted to the skin. Conversely, skin lymph nodes did not become more tolerogenic if transplanted to the intestine. The HZI scientists made these discoveries together with their colleagues from Prof. Oliver Pabst’s team at the Hannover Medical School (MHH).

Based on their observations, the scientists deduced that lymph node location influences the maturation process of the cells they contain. “The cells retained their original skills for weeks following the transplant,” says Dr. Sascha Cording. “You might say lymph nodes have something like a location-specific memory.”

And this in spite of the fact that all the various types of blood cells within a lymph node, including the immune cells, are constantly replaced, which means the lymph nodes’ location memory must be encoded somewhere in its stroma.

Additional experiments allowed the scientists to probe just how lymph nodes obtain their memory: Following birth, both the supply of vitamin A and the intestinal bacterial microflora figure prominently into this process. Without these two influencing factors, the lymph nodes simply forget about their origin and lose their tolerogenic properties.; Source: Helmholtz Centre for Infection Research (HZI)