Subset of T Cells Has Specialized Role in Early Stages of HIV, Researchers Determine

Mucosa-associated invariant T cells (MAIT cells) are a subset of the T-cell population. Their function and activity during the acute stage of HIV infection adds to the knowledge of immune system activation at this stage and could lead to possible new treatment interventions.

This was the conclusion researchers from the Karolinska Institutet in Sweden and Walter Reed Army Institute of Research reached after investigating the roles of MAIT cells in HIV, an area previously not investigated in depth. MAIT cells typically serve as bacterial bodyguards at the skin and mucous membranes, but when HIV overwhelms the immune system, they also respond, likely because of the infiltrating bacteria.

Using data on 29 individuals with acute HIV-1 infection from the RV217 Early Capture HIV Cohort Study, the study looked into their MAIT cell dynamics pre-infection, within days of the first positive results for HIV-1 RNA, and years into chronic infection. One of the most important functions of the MAIT cells that the researchers were able to pinpoint was their subset differentiation in acute and early HIV-1 infection. A decline in the frequency CD8+ MAIT cells was counterbalanced by a frequency gain by double negative MAIT cells, those that don’t have CD4, CD8, or natural killer markers.

In addition, the MAIT cell function cycle over the course of acute HIV-1 infection can be described in 3 steps:

1. Initial activation and expansion correlate with peak HIV-1 viremia
2. Elevated function during viral replication
3. Functional decline at onset of chronic infection

Their function can be somewhat restored with combination antiretroviral treatment (ART), but their numbers do not recover after ART, the authors noted. However, these numbers also do not drop as quickly as previously thought. Their results indicated they don’t even drop in the first year after infection with HIV.

“There is thus a fairly generous window of opportunity to preserve this important arm of anti-microbial immunity by initiation of treatment within this period, but this ultimately needs to be explored to better understand how early therapy can ameliorate immune dysfunction,” they stated.

Coming to a greater understanding of how MAIT cells function in the early stages of HIV could be an inroad to deeper understanding of antimicrobial immunity and possible interventions, they determined.

Reference

Lal KG, Kim D, Costanzo MC, et al. Dynamic MAIT cell response with progressively enhanced innate-like features during acute HIV-1 infection. Nat Commun. 2020;11(1):272. doi: 10.1038/s41467-019-13975-9.