Japanese investigators from the RIKEN Research Institute developed artificial lymph nodes (aLNs) outside of the normal lymphatic system, and have demonstrated strong immune functionality of aLNs when they transplanted newly created lymph nodes into immunodeficient mice. Such research might have major implications for our ability to deal with a range of disorders, such as HIV/AIDS and other infections, cancer, and autoimmune diseases.
The researchers, from RIKEN’s Research Center for Allergy and Immunology in Yokohama, constructed their mouse aLNs by impregnating a two- to three-millimeter-diameter scaffold of the fibrous structural protein collagen with connective tissue extracted from the thymus of newborn mice and dendritic cells. Earlier work suggests that it is the connective tissue stromal cells which organize the structure of lymph nodes.
The aLNs were 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.
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 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- 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.”
Press release: Artificial lymph nodes induce strong immune response …