Th17 Immune Cells in vivo: Friend or Foe?

In vivo, Th17 cells gave rise to Th1-like cells and also self-renewed and persisted as IL-17A-secreting cells. Th17 cells are not always short-lived or senescent, in fact,  some are a less-differentiated subset capable of superior persistence and functionality.

In vivo, Th17 cells gave rise to Th1-like cells and also self-renewed and persisted as IL-17A-secreting cells. Th17 cells are not always short-lived or senescent, in fact, some are a less-differentiated subset capable of superior persistence and functionality.

Upon encountering an antigen, T cells bearing CD4+ (a helper marker) proliferate and become polarized. During this process, the cells produce specific signaling molecules called cytokines.  This signaling stimulates the T cells to become more specialized.  What results is the production of T cell subsets such as Th1, Th17, or others.

Each different pattern of signaling molecules yields a different subset of T cells that are at various points along the path to T cell maturity and senescence.   Where the T cell sits along this path influences its ability to sustain survival long enough to become a CD8+ (a memory marker) T cell, which is able to respond to a secondary antigen challenge.

One of the subsets of T cells called the Th17s has developed a bad reputation for enabling cancer’s growth. Based upon in vivo models of maturing T cells, researchers labeled Th17s as tumor promoters because they secrete IL-17A and IL-17F, cytokines implicated in promoting tumorigenesis, especially at early stages of cancer development. Also, Th17s in vivo phenotypically resemble terminally differentiated T cells, so scientists expected their lifespans to be limited, making them unlikely candidates for becoming memory T cells.

Th17s reputation may now be improving, however. CCR’s Nicholas Restifo, M.D., and Pawel Muranski, M.D., recently reported in Immunity in vivo findings that point to a quite different role for these  immune cells. Working with their collaborators, they showed that, in vivo, in addition to sharing very similar gene expression profiles with immature immune memory (CD8+) T cells, Th17s express high levels of Tcf7, a protein that is a direct target of the Wnt/β-catenin axis.  This Wnt signaling network drives T cells toward specific points along their maturity pathways. 
Restifo and his collaborators discovered that Th17s in vivo are actually “early” memory T cells that can generate a Th1-helper-like subset of cells, which are capable of secreting large quantities of the cytokine interferon (IFN) γ and signaling for the elimination of cancer. Th17s also self-renew and secrete additional cytokines.

Following in vivo adoptive transfer, Th17 cells massively expanded, engrafted, and persisted. So rather than promoting oncogenesis, Th17s actually tackle cancer by generating Th1-helper-like cells that rally additional immune cells against cancerous growths.  This makes Th17s more friend than foe in the battle against cancer.

Summary Posted: 12/2011

Reference

Th17 Cells Are Long Lived and Retain a Stem Cell-like Molecular Signature. PubMed Link