In the presence of activated CD8 T cells, monocytes develop into a subclass of cells known as Tip dendritic cells (stained here with hematoxylin and eosin)
The immune system is a hectic, crowded environment, with various cells relaying messages to one another via molecules known as cytokines and chemokines. Unraveling this communication process can be difficult—like eavesdropping on a single conversation in a loud, crowded room. Fortunately, carefully designed cell culture experiments can help scientists to figure out how subsets of immune cells selectively respond to different threats.
Siew-Cheng Wong at A*STAR’s Singapore Immunology Network, David Kemeny at the National University of Singapore and co-workers have now clarified key steps in T helper cell type 1 (Th1) response. “Th1 response is the main arm of the cell-mediated immunity that is effective against intracellular bacteria, viruses and tumors,” explains Wong.
The researchers previously showed that CD8 T cells—also known as killer T cells for their role in destroying infected or cancerous cells—induce dendritic cells (DCs) to release a cytokine called IL-12p70 to promote Th1 response. In their most recent study, they sought to determine if this model was also applicable in the human immune system.
They found that human cells behave in a very similar fashion: when activated by bacterial toxins, human CD8 T cells interact with DCs and promote the release of IL-12p70 and other inflammatory cytokines and chemokines. However, the researchers found that the interaction between these cells leads to the secretion of additional factors that could promote differentiation of monocytes, the precursor of DCs, into a specialized cellular subtype known as TNF/iNOS-producing (Tip) DCs (pictured).
Tip-DCs help fuel the activation and proliferation of CD4 helper T cells. These key players in the Th1 pathway act in part via the secretion of high levels of interferon γ (IFN-γ), a cytokine that stimulates inflammatory response. “It was interesting to us that Tip-DCs may potentially sustain Th1 responses through their ability to prime CD4 T cells for IFN-γ production,” says Wong.
These findings are in keeping with the results from previous studies, which have shown that Tip-DCs contribute to elimination of the influenza virus and Listeria bacteria, but may also fuel the immune overreaction in psoriasis. “It seems that Tip-DCs may participate in the clearance of pathogens in general, but their presence may also contribute to excessive inflammation in certain disease contexts,” says Wong. “We are now examining the function of Tip-DC in contact hypersensitivity, a condition in which the immune system overreacts to chemical exposure.”
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network.
