T Cells Work Like Local Militias, Not National Army

The immune system is often likened to a national defense force, roaming the entire body on the lookout for pathogens to destroy.

But a new study by P&S immunologists shows that the immune system’s T cells act more like localized militia and are far more restricted than previously thought.

“By mapping the locations of T cells throughout the body, we’ve found that each organ has its own set of resident T cells that are specifically adapted to the local pathogens and conditions,” says the study’s senior author Donna Farber, PhD, professor of surgical sciences (in surgery and in microbiology &immunology) in the Columbia Center for Translational Immunology.

Such localization hasn’t been appreciated before, Dr.  Farber says, because most of what we know comes from studies of T cells in blood. “But organs like our lungs, intestines, and the skin are constantly exposed and we need immune cells at these sites,” she says. “Blood contains only a very small fraction—two percent—of our T cells.”

Blood, of course, is easier to obtain than organs, so Dr. Farber turned to a team of Columbia surgeons and the New York Organ Donor Network (NYODN).  Through its collaboration with the NYODN, Dr. Farber’s team has access to organs and tissues from organ donors from whom consent for the use of organs for research has been obtained. The current study represents an analysis of organs and tissues from 56 different individuals, with ages spanning six decades. This resource has enabled an unprecedented examination of how T cells are organized and maintained throughout the body.

In the lab, graduate students and first authors Joseph Thome and Naomi Yudanin identified the type of T cells occupying each organ. These types include naïve cells that respond to new pathogens and memory cells that retain information on previously encountered pathogens and can mediate protective immunity to pathogens.

They found that each organ had its own unique collection of T cell types—which proved surprisingly similar among all individuals.

“The immune system in different lungs were more similar to each other than to another organ in the same person,” says Dr. Farber. “These individuals were as diverse as New York City, but each tissue had a similar complement of T cells adapted in the same way.”

Sites such as lungs and intestines, the point of entry for many pathogens, contain complements of memory T cells constantly on alert to maintain health in these sites. These “localized militias” of the immune system establish themselves early in life and maintain themselves in stable form for decades.

A finer analysis looked at different pathogens encoded in the memory cells in each organ. Though this analysis could not identify pathogens by name, it could determine if the same pathogen was remembered in different organs.

Here, too, organs were unique. “Within a person, you store up memories that are specific to each site,” Dr. Farber says.

That degree of compartmentalization of the immune system’s T cells will be surprising to most immunologists, Dr.  Farber adds.

And the findings are sure to impact the design of certain vaccines and cancer immunotherapies.

“We need to understand what’s happening locally. For a vaccine, if you know that a pathogen is always going to enter the lung, that’s where you want to beef up immunity. For cancer therapy, tumors appear in tissues, you need to understand the local tissue.”