How these “resident” memory T cells are generated was unknown, and their importance with regard to how our immune system remembers infection and how it prevents against re-infection is being studied intensively.
Now, a study by a Brigham and Women’s Hospital (BWH) research team led by Xiaodong Jiang, PhD, research scientist and Thomas S. Kupper, MD, Chair of the BWH Department of Dermatology, and the Thomas B. Fitzpatrick Professor of Dermatology at Harvard, has used a model involving a vaccinia virus infection of the skin to answer important questions about how these newly discovered cells protect us.
The study will be electronically published on February 29, 2012 in Nature.
Jiang and Kupper used skin infection with vaccinia virus to study the relative roles of central memory T cells (T cells that circulate in the bloodstream) and resident memory T cells in protective immunity. What they found was that after infection, disease-specific T cells were rapidly recruited not only to the infected site, but also to all areas of skin.
They further showed that multiple additional infections at future time points led to an accumulation of even more of these resident memory T cells in the skin, and that these cells remained in the skin for long periods of time.
Finally, Jiang and Kupper showed, for the first time, that resident memory T cells were the most important protective immune cells in fighting infection—much more important than central memory T cells, which were ineffective at rapid immune protection by themselves.
“Finding that resident memory T cells were so much more important than central memory T cells in protective immunity was surprising, and makes us re-think current immunologic dogma,” said Kupper.
While skin was used as a model system in this study, the results can be extrapolated to the lungs, GI tract, and other epithelial tissues that contact the outside world.
The findings suggest that the most important elements of T cell memory to infectious diseases may reside in tissues, rather than in the blood.
“The immune system provides the right T cells, at the right place and time, to protect us from an environment that is full of potentially harmful pathogens.” said Kupper.
Also, the findings imply that vaccines should be optimized to create precisely this kind of long lasting tissue-resident T cell immunity, and that the current focus on antibody production may not be as important.
“This work suggests a fundamental reassessment of how vaccines are both constructed and delivered,” said Kupper. “These results have altered the way we think about the immune system and vaccination for infectious diseases.”
This research was supported by grants from the National Institutes of Health.
Brigham and Women’s Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies and the Women’s Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.
Marjorie Montemayor-Quellenberg, (617) 534-2208, [email protected]