T cells are vital components of the immune system, with conventional T cells playing a central role in adaptive immunity and unconventional T cells having additional functions similar to both innate and adaptive immunity, such as involvement in stress responses and tissue homeostasis. Unconventional T cells are a diverse and underappreciated group of relatively rare lymphocytes that are distinct from conventional CD4+ and CD8+ T cells, and that mainly recognize antigens in the absence of classical restriction through the major histocompatibility complex (MHC). Now, researchers at the Julius Maximilian University (JMU) of Würzburg in Bavaria, Germany, have discovered that so-called unconventional T cells continuously migrate from the tissue into the lymph nodes and influence the immune responses there.

Their findings are published in the journal Immunity in an article titled, “Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes.” The study was led by Wolfgang Kastenmüller, MD, professor at JMU.

“Lymphatic transport of molecules and migration of myeloid cells to lymph nodes (LNs) continuously inform lymphocytes on changes in drained tissues,” wrote the researchers. “Here, using LN transplantation, single-cell RNA-seq, spectral flow cytometry, and a transgenic mouse model for photolabeling, we showed that tissue-derived unconventional T cells (UTCs) migrate via the lymphatic route to locally draining LNs.”

“Each tissue in our body has different subtypes of unconventional T cells,” explained Kastenmüller. “Since these cells each migrate to the nearest lymph node, the individual lymph nodes also differ in the composition of the T cells. And that has a direct effect on the immune responses of the individual lymph nodes.”

“By making use of single UTC lineage-deficient mouse models, we found that UTCs functionally cooperated in interconnected units and generated and shaped characteristic innate and adaptive immune responses that differed between LNs that drained distinct tissues,” wrote the researchers.

Their findings demonstrate that lymphatic migration of UTCs is a key determinant of site-specific immunity which has potential implications for vaccination strategies and immunotherapeutic approaches.

“That is why we want to investigate next whether we can use the difference in lymph nodes to make vaccinations more efficient or to improve immunotherapies against cancer,” said Kastenmüller. Another interesting question is whether the differences in the lymph nodes can be actively influenced. And it is to be clarified what significance the new findings have with regard to the development of autoimmune diseases and cancer.