If someone who has TB coughs in a room full of people, why is it that only some of the people in the room will get infected? And of those who get infected, why will only some become ill but others never be bothered by TB?

These are some of the questions that Emily Wong, a K-RITH Research Associate and Instructor in Medicine at Harvard Medical School, is hoping to answer through her research into a novel subpopulation of T cells, called Mucosal-Associated Invariant T (MAIT) cells.

Simply put, T cells are usually part of the adaptive or acquired immune system. MAIT cells are exciting because they bridge the adaptive and innate immune systems and have some innate-like properties. “We’re interested because they hang out in the lungs,” says Dr Wong. “They may be part of the very early response to tuberculosis; that’s our hypothesis. Potentially, they could make a difference in whether an exposure to TB results in an infection or not.”

“We want to figure out what’s going on in the lungs of people who have good protection against TB and try to boost those responses in people who are at risk for getting infected — like people with HIV. That’s the kind of vaccine strategy we’d be interested in contributing to.”

To help fund the next steps of this collaborative, multidisciplinary work, Dr Wong together with Dr Alex Shalek from the Massachusetts Institute of Technology have just been granted a Harvard University Centre for AIDS Research (CFAR) award. The 12-month grant will specifically support the establishment of a platform to perform single cell RNA-sequencing and TCR sequencing.

Wong was also recently awarded a five-year Mentored Clinical Scientist Research Career Development Award from the US National Institutes of Health (NIH). This grant is usually only available to those based at a US institution, but Wong said she was pleased that the NIH understood that the work she wants to do can only really be done at K-RITH. Investigator Thumbi Ndung’u is supervising her research, which is already off to an exciting start.

“We’ve been collecting lung fluid samples with our colleagues at Albert Luthuli Central Hospital and analysing them by flow cytometry. We’ve looked at the surface characteristics of groups of cells and found some intriguing patterns, but it’s hard to say exactly what these patterns mean.” To try to figure this out they have started to collect the genetic material from the cells to analyse their T cell receptors and gene expression patterns. “We’re also starting to separate the cells and look at each one individually. This allows us to figure out the differences between cells within the same population. Using this approach we are already seeing things that are getting us excited.”

Last month, Wong attended the first Immune Profiling in Health and Disease Conference in Seattle, Washington and presented some of this work. “The field is going through a rapid period of discovery as high-throughput genetic sequencing is being used for the study of immune responses. The clinical samples we have been collecting and our ability to sort TB-infected samples safely in the BSL-3 here at K-RITH allow us to apply these approaches to the intersection of HIV and TB immunity. It’s exciting to come to work every day. It’s very, very exciting.”