Students Led By Dr. Zhibin Chen Make Immunology Discovery

University of Miami Miller School of Medicine Ph.D. student Jen Bon Lui, in collaboration with medical student Sarah Teplicki and Ph.D. graduate Priya Devarajan, are celebrating the success of a cellular immunology discovery. Led by Zhibin Chen, Ph.D., associate professor of microbiology and immunology, the team has found that in the large intestine environment, CD8 T cells, commonly known as immune system killer cells, can become a special type of protector CD4 T cells. Their findings are published in the February issue of Cell Report.

“The discovery of CD8 T cells converting to CD4 T cells is exciting because of its many potential applications in immune-related diseases,” said Lui. CD4 T cells can regulate inflammatory damage to the intestine.

“What we discovered is not just offering a philosophical perspective,” Chen said, “but novel therapeutic possibilities. It may be relevant to a number of clinical conditions, including autoimmune diseases, cancer, transplantation and HIV/AIDS.”

Every person has a unique immune system that can discriminate between an individual’s own “self” cells and “non-self” foreign cells. However, the immune system also has to distinguish between enemy and friendly “non-self” bacteria, the latter known as microbiota, much of which resides in the gut. The body depends on microbiota to be healthy, so it is necessary for the immune system to create a harmonious relationship with friendly bacteria instead of identifying these cells as foreign.

Because the body is capable of facilitating immune balance, Lui, Teplicki, Devarajan and Chen hypothesized that in addition to the “self” and “non-self” mode of discrimination, the immune system must also be capable of seeing cells in a “selfless” way at the interface with friendly bacteria. To test the hypothesis, they examined T lymphocyte differentiation in the large intestine environment, tracking the fate of two clones in the CD8 T lineage and two clones in the CD4 T cell lineage that are not specific to food antigens or microbiota. What they discovered was unexpected.

In the large intestine environment, CD8 T cells adapted by becoming special protector CD4 T cells, known as Treg cells. In addition, the discovered Treg cells recognized MHC class I, which are expressed by most human cells, as opposed to the previously characterized Treg cells, which recognized MCH class II, conveyed only by rare types of cells in the immune system.

“We didn’t mean to discover this type of cell adaptation,” Chen said. “Our study was originally designed to test our hypothesis of a ‘selfless’ mode of immune tolerance induction. Imagine our surprise when we realized that we were seeing CD8 T cells cross differentiating to CD4 Treg cells, particularly because CD4 Treg cells can effectively control damage to healthy tissues in autoimmune diseases and transplantation settings.”

The implications are huge for future research and ultimately the treatment of many diseases. The next step for the team will be to identify the signals triggering the adaptation of T cell lineages and to also generate these cells in a lab setting.

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