Interleukin-7 as a potential therapeutic strategy to reconstitute MAIT cells (#86)
Mucosa-associated invariant T (MAIT) cells are antimicrobial innate-like T cells present in peripheral blood, lung, liver and mucosal tissues of humans. MAIT cells are defined by a semi-invariant T cell receptor (TCR) a-chain, are restricted by the major histocompatibility complex (MHC)-related protein 1 (MR1). Individuals with chronic HIV-1 infection have low frequencies and functional impairment of MAIT cells, and these deficiencies are not restored with antiretroviral therapy (ART). Notably, MAIT cells express high levels of IL-7R (CD127), and IL-7 dramatically enhances the function of MAIT cells from both healthy individuals and HIV-infected patients in vitro. We hypothesized that in vivo administration of IL-7 in chronically HIV-1 infected patients on ART may overcome the inability of long-term ART alone to restore MAIT cells. To address this hypothesis, we evaluated the numbers, phenotype, and functionality of MAIT cells before and after IL-7 administration in chronically HIV-1 infected individuals on ART. Seven HIV+ subjects were treated with three subcutaneous injections of IL-7 and PBMCs were collected at baseline and at 12 weeks post IL-7 treatment. IL-7 led to an increase in the frequency of MAIT cells within total lymphocytes, compared to baseline. Furthermore, the absolute number of MAIT cells among the CD3+ cell population significantly increased at week 12 compared to baseline. Notably, there was a preferential expansion of the CD8+ MAIT cell subset. These results suggest that IL-7 may represent a therapeutic intervention for the restoration of MAIT cells in chronic HIV-1 infection and in other conditions associated with MAIT cell loss.