Rare immune cells found to play a major role in lasting immunity

By Dr. Ananya Mandal, MDApr 1 2012

According to the latest research from the Walter and Eliza Hall Institute the characterization of a rare immune cell’s involvement in antibody production and ability to ‘remember’ infectious agents could help to improve vaccination and lead to new treatments for immune disorders.

Dr Stephen Nutt and Dr Katja Lüthje were part of a research team that discovered a rare cell type, called T follicular helper cells, are needed for antibody production and long-lasting 'memory' of infectious agents. The found that the cells, called T follicular helper cells, represent less than half of one per cent of all immune cells, but play a critical role in antibody production and developing long-lasting immunity. However, the cells are also dramatically increased in chronic inflammatory disease, suggesting that they could be a therapeutic target for treating these diseases.

The team led by Dr Katja Lüthje and Associate Professor David Tarlinton, from the institute’s Immunology division, and Dr Stephen Nutt from the institute’s Molecular Immunology division, discovered a means of identifying the rare T follicular helper cells while they are actually involved in instructing the immune response. This showed the possible fates of these cells. Dr Luthje said the scientists used a special fluorescent protein to help identify which cells were involved in the antibody production process. The research was published today in the journal Nature Immunology.

Dr Lüthje explained that the T follicular helper cells were essential for developing strong and specific antibody responses to infectious agents. “Antibodies are fundamental to the body’s defense against infection,” Dr Lüthje said. “Antibody production critically relies on the interaction of two cell types: B cells that produce antibody, and helper T cells that recruit and ‘teach’ the B cells how to respond to infectious agents. In this study, we used a special fluorescent protein to help identify exactly which cells were involved in the process, and discovered that, amongst the rare T follicular helper cells, only a subset were actively involved in instructing B cells in antibody production.”

“The success of vaccines relies on antibody production and long-term immune memory - without these, most routinely-used vaccines, including measles, mumps and tetanus, do not work,” Dr Nutt said. “It is well established that antibody-producing B cells can remember a particular infectious agent and rapidly respond if and when they come across it again. Our study shows, for the first time, that (T cells) also develop memory to rapidly respond to infection.”

The discovery would be hugely important for the future development of vaccines, which rely on immune memory to prevent subsequent infections, Dr Nutt said. “Some vaccines, such as polio are very effective at establishing long-term immunity, while others, such as the cholera vaccine are not particularly effective and need ongoing boosters,” he explained. “It may be that the vaccines are not establishing good (T cell) memory, and this could be something to look at for developing new vaccines for diseases that currently do not have good preventive treatments.”

Associate Professor Tarlinton said another key finding was that T follicular helper cells show a remarkable flexibility in their role in immunity. “We found that T follicular helper cells are pretty flexible, adapting to carry out several different functions depending on where they are needed,” he said.

He said the research team also discovered that T follicular helper cell numbers are tightly controlled by the immune system, which might explain why increases in their numbers are associated with chronic inflammatory diseases, which include rheumatoid arthritis, type 1 diabetes, lupus and multiple sclerosis. “In some models, a large increase in the numbers of T follicular helper cells is associated with the development of chronic inflammatory, or what we call autoimmune, diseases in which the immune system attacks its own tissues,”

The research was supported by the National Health and Medical Research Council of Australia, the Sylvia and Charles Viertel Foundation, the German Academic Exchange Service, Pfizer Australia Research, the Australian Research Council and the Victorian Government.