Abstract
HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.
Highlights
A progressive loss of CD4+ T lymphocytes from blood, lymphoid organs and mucosal tissues is the hallmark of Human Immunodeficiency Virus 1 (HIV-1) infection
As described among CD4+ lamina propria lymphocytes (LPLs), T lymphocytes subset producing IL-17 (Th17) are preferentially depleted from the gut of people living with HIV (PLWH) and this loss above, among CD4+ LPLs, Th17 are preferentially depleted from the gut of PLWH and is considered a major cause for microbial translocation, chronic immune activation, and this loss is considered a major cause for microbial translocation, chronic immune activainflammation in both treated and untreated PLWH [2]
Inconsistencies in study designs and patients selection, there is a consensus about the inability of antiretroviral therapy (ART) in reconstituting the pre-infection immunological is a consensus about the inability of ART in reconstituting the pre-infection immunologimilieu, with particular reference to Th17 lymphocytes frequencies and functionality [20]
Summary
A progressive loss of CD4+ T lymphocytes from blood, lymphoid organs and mucosal tissues is the hallmark of Human Immunodeficiency Virus 1 (HIV-1) infection. Such continuous depletion of CD4+ T lymphocytes leads to the acquired immune deficiency syndrome (AIDS) if specific antiretroviral therapy is not addressed promptly [1]. The gut hosts the gut-associated lymphoid tissue (GALT) and is believed to contain the large majority of the CD4+ T lymphocytes in the human body [3] Within such scenario, a pivotal role is exerted by a specific CD4+ T lymphocytes subset producing IL-17 (Th17) [4], which are CD4+ T cells specialized in helping to maintain mucosal integrity and antimicrobial inflammatory responses [5].
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