Most of our organs stay in place. The immune system is different. It moves, it migrates, it ebbs and flows. Our immune systems are made up of free agent cells that can go to almost any organ and release proteins and compounds that kill viruses, bacteria and infected cells. Some of these free agents live in the spleen or the lymph nodes. Some just troll around in the blood looking for pathogens or signals and will go back to these organs or die if they can’t find anything interesting.
There are two kinds of cells that can live a lot longer; even throughout your lifetime. They start out as B cells or T cells. (B cells come from the bone marrow originally and T cells from the developing thymus.) B and T cells adapt themselves to specific parts of invading viruses and bacteria, so they’re called “adaptive immune cells.” Some become memory cells after this adaptation, meaning they can respond with a vengeance if they see the same pathogen coming around a second time. This is the basis for vaccination.
Memory cells need a place to live. Some live in the spleen and some B cells go back to their roots in the bone marrow to live out their days in peace. It’s been thought that memory T cells just float around in the body as rouge patrollers and quickly arrive at an organ whenever a repeat offender like the flu rears its ugly head. But recently, Donna Farber and her lab at Columbia University reported that those reacting memory T cells found at a site of re-infection had been there since the first infection. They were residents of the lungs and they were very different from the memory T cells in the blood and spleen.
The idea makes sense. The most effective and well-adapted T cells are ready to meet the offending virus on its turf, in this case the lungs. This work, like much immunology, was done in mice, which raises the question, What does this mean for humans, or for vaccine development? Scientists know so much about the “where and when” features of immune responses because we can pull out any mouse organ at any time and look for any type of cell. We can count them, classify them, collect them and inject them into another mouse. You name it, it can be done.
Human immunology, for obvious reasons, can’t be done this way. Most work done on human immune cells is done with blood samples. So if memory T cells in organs are fundamentally different from those in the blood, as Dr. Farber’s work suggests, we really only have half the picture. And it may not even be a very accurate half.
Dr. Farber saw that if we mean to understand the human immune system, our methods have to change. She initiated a collaboration with the New York Organ Donor Network and her lab has been able to process fresh samples from otherwise healthy brain-dead donors to study the true distribution of immune cells in the human body. The group initially described T cells in the lungs, intestines, spleens, lymph nodes and blood of 24 donors. The study wasn’t important because of any complicated experiments or newly discovered drug targets, but because it lays out groundwork that has never before been possible.
Biopsy tissues from sick patients (often people with immune diseases) have been the mainstay for immunologists doing human work. The subjects in this study were mostly healthy because they were cleared to be organ donors. The care taken with the tissues and the speed with which they were processed allowed Farber and her group to do more than look at the tissues under a microscope; they were able to culture them and test their functionality. The arrangement also meant that this was the first time multiple tissues taken from the same donor at the same time could be used for immunology studies.
Dr. Farber’s work is providing physicians and immunologists with a picture of the steady state immune system that has never before been available. And collaborations with other immunology specialists will address other subsets of immune cells in the same tissues. Recently, her group demonstrated that memory T cells against flu live in specific niches along the airways of human and mouse lungs.
The author of a commentary on Farber’s work brought up a 16th century physician named Vesalius, the first to promote post-mortem dissection in a time when the prevailing knowledge of human anatomy was based solely on animal dissection. Even as our understanding of the mouse immune system grows and becomes more complex, there is huge value in stepping back and defining the basics of the human immune system.
Teijaro J.R., Turner D., Pham Q., Wherry E.J., Lefrancois L. & Farber D.L. (2011). Cutting Edge: Tissue-Retentive Lung Memory CD4 T Cells Mediate Optimal Protection to Respiratory Virus Infection, The Journal of Immunology, 187 (11) 5510-5514. DOI: 10.4049/jimmunol.1102243
Sathaliyawala T., Kubota M., Yudanin N., Turner D., Camp P., Thome J.C., Bickham K., Lerner H., Goldstein M. & Sykes M. & (2013). Distribution and Compartmentalization of Human Circulating and Tissue-Resident Memory T Cell Subsets, Immunity, 38 (1) 187-197. DOI: 10.1016/j.immuni.2012.09.020