Study: Trait of Rare Few Whose Bodies Naturally Control HIV Have 'Trained' Immune Cells

A recent study published in the Journal of Clinical Investigation showed that elite controllers, a rare subset of people whose immune system can control HIV without the use of drugs, have myeloid dendritic cells, part of the innate immune response, that display traits of a trained innate immune cells.

“Using RNA-sequencing technology, we were able to identify one long-noncoding RNA called MIR4435-2HG that was present at a higher level in elite controllers’ myeloid dendritic cells, which have enhanced immune and metabolic states,” said Xu Yu, MD in a press release. “Our research shows that MIR4435-2HG might be an important driver of this enhanced state, indicating a trained response.”

The primary job of myeloid dendritic cells is to support T cells, which are key to the ability to control HIV infection. Because MIR4435-2HG was found in higher levels only in cells from elite controllers, it may be part of a learned immune response to infection with HIV, according to the study.

Further, myeloid dendritic cells with increased MIR4435-2HG also had higher amounts of a protein called RPTOR, which drives metabolism. This increased metabolism possibly allows the myeloid dendritic cells to better support the T cells that control HIV infection, according to the study.

“We used a novel sequencing technology, called CUT&RUN, to study the DNA of these cells,” said study author Ciputra Hartana, MD, PhD, in the press release. “It allowed us to study epigenetic modifications like MIR4435-2HG, which are molecules that bind to the DNA and change how, or if, the DNA is read by the cell’s machinery.”

The researchers found that MIR4435-2HG might work by attaching to the DNA near the location of the RPTOR gene. The bound MIR4435-2HG would then encourage the cell’s machinery to make more of the RPTOR protein, using the instructions found in the RPTOR gene. This type of epigenetic modification, or trained response to HIV infection, would allow the myeloid dendritic cells to stay in an increased metabolic state, and therefore provide long-term support to the T cells fighting the virus, according to the study.

“Myeloid dendritic cells are very rare immune cells, accounting for only 0.1-0.3% of cells found in human blood,” Yu said in the press release. “We were fortunate and thankful to have access to hundreds of millions of blood cells from the many study participants who have donated their blood to support our HIV research. These donations were key to making this discovery.”

REFERENCE

A trait of the rare few whose bodies naturally control HIV: “trained” immune cells. Massachusetts General Hospital. Published May 4, 2021. Accessed May 6, 2021.