Going Local

The human immune system—popularly conceived along the lines of a roaming national defense force, poised to combat pathogens—has its own variation on the mantra location, location, location.

“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 Donna Farber, PhD, professor of surgical sciences (in surgery) and of microbiology & immunology in the Columbia Center for Translational Immunology. Such specialization has not been appreciated, Dr. Farber says, because most of what is known about T cells comes from studies of those circulating in the blood. T cells also populate such organs as lungs, intestines, and skin, which are constantly exposed to pathogens. “We need immune cells at these sites, too,” she says. “Blood contains only a very small fraction—2 percent—of our T cells.”

Blood, of course, is relatively easy to obtain for research purposes. For T cells from other body systems, Dr. Farber turned to the New York Organ Donor Network (LiveOnNY), which granted Dr. Farber’s team access to biological samples from organ donors for which consent for use of tissues for research was obtained. The team analyzed T cells from 56 individuals, with ages spanning six decades.

In the lab, graduate students and first authors Joseph Thome and Naomi Yudanin identified the type of T cells in 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 that proved surprisingly similar among all individuals. “The immune systems 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 persist in stable form for decades.

A finer analysis looked at the antigen-specific receptors expressed by memory cells in each organ, investigating whether the same T cell clone (which would recognize the same antigen) was present 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, she adds. And the findings are sure to inform clinical applications. “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.”

This is a summary of research published in Cell, Nov. 6, 2014.