A new study led by MHRP has shown that a subset of T cells called mucosa-associated invariant T (MAIT) cells respond dynamically during acute HIV, and the functionality of these cells changes as infection progresses to become more innate-like. Findings were published today in Nature Communications.
MAIT cells are found abundantly in mucosal tissues, blood and the liver. MAIT cells suffer numerical and functional loss in chronic untreated HIV infection, but the timing of this loss is unknown. In the new study, researchers examined samples from MHRP’s RV217 Early Capture HIV Cohort study, which characterizes the acute stages of HIV infection, and found that MAIT cells are activated and actually expand in the first couple weeks of infection. Decline in MAIT cell quantity occurs much later than originally hypothesized, beyond one year in untreated infection.
Furthermore, the study demonstrated that during acute infection, MAIT cell function is elevated as viral replication is controlled to a set-point level and later declines at the onset of chronic infection. Surprisingly, MAIT cells appear to develop enhanced innate characteristics as infection progresses.
“HIV infection impairs the immune system’s ability to respond to microbial pathogens and MAIT cells represent one of many casualties leaving the host susceptible to bacterial co-infections,” said Dr. Michael Eller, head of flow cytometry at MHRP and senior author of the publication. “Our study shows that this does not happen as early in infection as we anticipated. Future studies will tell us if early ART may preserve the amount and quality of MAIT cells.”
Researchers integrated cutting edge flow cytometry and transcriptomics to better understand MAIT cell activity. The RV217 acute cohort represents the only opportunity to study these cells in early untreated acute infection.
The ambitious RV217 study began in 2009 and prospectively followed a group of high-risk volunteers in East Africa and Thailand, tracking HIV status and characterizing progression through the acute stages of HIV infection. Volunteers were enrolled before they began to show detectable HIV antibodies, and if they became infected, researchers were able to capture samples from the earliest stages of HIV infection – in some cases within days. RV217 provided the first characterization of acute HIV infection, and the New England Journal of Medicine publication stemming from the study has been cited more then 130 times. The study concluded in 2018, but MHRP scientists are still using samples from the study to explore immune responses during early acute infection.