Insights into tissue-based T cells

US researchers have, for the first time, characterized T cells located in human tissues, rather than in the blood.

"Most of what we have known about human T cells is based on studies of the blood, because it is so accessible," said lead researcher Donna Farber (Columbia University Medical Center, New York) in a press statement. "But that is only a small sampling of the body's T cells."

The team analyzed tissues from 24 organ donors aged between 15 and 60 years, revealing compartmentalization of T cells that was "remarkably consistent in diverse individuals."

All tissue-based T cells bore the activation marker CD69, distinguishing them from circulating T cells, Farber et al report in Immunity.

They examined T cells from the donors' blood and from eight different tissues: spleen; inguinal, lung, and mesenteric lymph nodes; lung; jejunum and ileum; and colon. The donors were all free of HIV or any chronic or immunological condition, and had died suddenly of traumatic causes, including traffic accidents, suicide, and stroke.

In the donors' spleens, the proportions of T and B cells were roughly equal, whereas T cells outnumbered B cells at all other sites, ranging from a two- to fourfold increase in blood and lymph nodes to a 20-fold increase in the jejunum. CD4-positive T cells predominated at most tissue sites, except at the intestinal sites, where the proportions of CD4- and CD8-positive cells were fairly equivalent.

The donors' blood had similar proportions of memory T cells and those that were either naïve or terminally differentiated (effector cells). By contrast, memory T cells were predominant at all tissue sites, particularly at mucosal sites where they accounted for more than 90% of T cells, and this predominance rose with the age of the donor. The increasing prevalence of memory T cells with age was limited to CD4 cells, with the proportion of memory CD8 cells remaining constant throughout life.

Throughout the body, therefore, memory CD4 cells were the most abundant type of T cell.

The majority of T cells at the eight tissue sites were quiescent; in other words, they did not secrete cytokines when stimulated. The next most common T-cell type was memory CD4 cells that produced interleukin (IL)-2 on stimulation. Cells that produced IL-17 were limited to mucosal sites, suggesting that mucosal-draining lymphoid tissues may be the site of local priming of IL-17-producing memory CD4 cells, says the team.

"To make better vaccines, it may be necessary to activate a T-cell response at the site of an infection, not just in the general circulation," commented Farber. "But first we have to know what types of immune cells are in those tissues and how they function. This is a first step in that direction."

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