T Cell Function Modulated by Lymph Node Acidity
ACTIVATION of T cells within lymph nodes is an important component of effective immunity, but recent research has shown that this activation may be regulated by the pH of the lymph node microenvironment.
Immune cell activation within lymph nodes triggers the production and release of antibodies, as well as T–cell activation. This process activates T cells in such a way that their effector function is not turned against the lymphatic system itself. Recent research aimed to identify characteristics of the lymph node environment that may affect this activation and protect the lymph nodes from the actions of the T cells.
Acidosis is known to inhibit T cell function; researchers at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA, assessed the acidity of lymph nodes using fluorescence and MRI techniques. “Oxygen levels are reported to be low in lymph nodes and that hypoxic tissue is acidic. We wanted to determine if lymph nodes were also acidic,“ explained study author Dr Robert Gillies. The researchers found that within lymph nodes there is a naturally occurring acidic niche, which the research team believe is generated by the T cells present in the lymph nodes.
Localised acidosis as a process of T cell function is an important part of the adaptive immune response, explained Dr Gillies: “The low extracellular pH of lymph nodes does not impair the T cell’s activation, but it does suppress the cytokine production, which is likely what protects lymph nodes from being attacked by the immune system.”
This physiological mechanism may be exploited by cancers and contribute to lymph node metastasis and the lymphatic spread of cancer. Future management strategies could also target this mechanism by manipulating lymph node acidity in combination with immunotherapies such as T-cell checkpoint blockade therapy; however, further research is needed.