Researchers from RIKEN Research Center for Allergy and Immunology in Japan research team, which earlier developed artificial lymph nodes, has recently shown that these artificial nodes can produce immune cells and strong immunological responses when transplanted into mice lacking a working immune system. Abstract.

This is an important step towards being able to strengthen or perhaps even replace human immune systems, particularly for fighting AIDS, cancer, and stubborn infectious diseases. According to project leader Takeshi Watanabe, the team wants to “make a prototype human model within two or three years."

By introducing artificial nodes bursting with robust T and B cells into AIDS patients, Watanabe believes he might be able to revitalize damaged immune systems. In terms of cancer, he envisions being able to adopt a similar approach, wherein the transplanted nodes will contain T cells targeted to track down the antigens produced by tumour cells and eliminate them.

How do They Do That?

Researchers first engineered mouse artificial Lymph Nodes (aLNs) by impregnating a two- to three-millimeter-diameter scaffold of fibrous structural protein collagen with connective tissue extracted from the thymus of newborn mice and dendritic cells.

Earlier studies suggested that it is the connective tissue stromal cells (connective tissue cells of an organ found in the loose connective tissue) which govern the structure of lymph nodes.

The aLNs were then initially implanted into mice with a normal, healthy immune system, which had previously been injected with a harmless antigen compound to trigger an immune response.

So the aLNs became populated with immune system T-cells and B-cells which specifically recognize and counter germs or cancer cells expressing the injected antigen.

Four Weeks of Antigen Response

These primed aLNs were then transplanted into two sets of mice; a group with a normal immune system which had never been exposed to the antigen, and a group in which the immune system did not function.

When the mice were then exposed to the antigen, both groups responded immediately by making appropriate protective antibodies, and the response to the antigen lasted for longer than four weeks, which means immune cells which retained memory of the antigen had been generated.

Further investigation of the immunodeficient mice showed that T-cells and B-cells from the aLNs migrated to their spleens and bone marrows and were there generating large numbers of antigen-specific antibody-forming cells. The results also revealed some of the compounds involved in directing this migration process.

The successful development of the aLNs in mice opens the way to producing customized lymph nodes impregnated with antibody-forming cells and other compounds specifically geared to treating certain conditions.

“That is our purpose," says Watanabe, “not necessarily to make replacements for natural lymph nodes, but rather more functional organs applicable to particular diseases and allergies."

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