HIV and Tuberculosis co-infection impacts T-cell activation markers but not the numbers subset of regulatory T-cells in HIV-1 infected patients

Abstract

BackgroundTuberculosis (TB) has been shown to accelerate the clinical course of HIV infection, but the mechanisms by which this occurs are not well understood. Regulatory T-cells (Tregs) are known to dampen hyperactivation of the immune cells, but it remains unclear whether hyperactivation of T-cells in HIV infection is associated with a decrease of Tregs and what the effect Mycobacterium tuberculosis (MTB) co-infection has on T-cell activation and Tregs.ObjectivesIn this study, we aim to evaluate whether active TB is associated with the increased expression of T-cell activation markers and reduced number of Treg cells in HIV-1-infected patients.MethodsThis study was conducted on 69 subjects consisting of 20 HIV-infected patients, 20 HIV and MTB co-infected patients, 19 MTB-infected patients and 10 uninfected control subjects negative for both MTB and HIV. The frequencies of T-cell activation markers (CD38 and HLA-DR) and Treg cells (CD4+CD25+CD127-) were measured by flow cytometry.ResultsSignificantly higher expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells was found in MTB and HIV co-infected patients compared with HIV-infected patients. However, no significant difference in the percentage of Treg cells was reported between HIV patients with TB and those without. The study also showed a negative correlation between regulatory T-cells frequency and CD4+ T-cell counts.ConclusionThese results suggest that TB enhances the expression of peripheral T-cell activation markers during HIV infection, whilst having no impact on the percentages of Treg cells.

Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8+ T cells in HIV/TB co-infection

“…Immune activation has been used as predictor of HIV disease progression [25], which has previously been shown with CD38 expression on CD8 + T cells [26]. Persistent infections reportedly impact HIV disease progression triggering excessive T-cell activation [15,27,28]. Here, we showed that increased expression of CD38 on T cells of HIV/TB co-infected compared to HIV-infected individuals, which is in line with others [27,29] as previously proposed due to peripheral immune activation [29].…”

“…Persistent infections reportedly impact HIV disease progression triggering excessive T-cell activation [15,27,28]. Here, we showed that increased expression of CD38 on T cells of HIV/TB co-infected compared to HIV-infected individuals, which is in line with others [27,29] as previously proposed due to peripheral immune activation [29]. TB had also reported to foster immune activation by increasing the expression of CD38 on T-cell subsets [30,31].…”

“…Correlation analysis showed that HLA-DR expression was directly associated with T-cell counts. Contrary to others [27,29], we showed that MTB may be involved in attenuating the expression of HLA-DR [32,33] although active TB could also suppress HLA-DR [34]. Based on this, we suggested that MTB to up-regulation of CD38 and down-regulation of HLA-DR in co-infection explaining the inconsistencies in CD38 + HLA-DR + CD4 + and CD8 + T-cell subsets of HIV/TB co-infected patients.…”

Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

“…Numerous literatures have established that immune activation is a direct measure of HIV disease progression [45,[59][60][61] , which has previously been shown with CD38 expression on CD8 + T cells [43,46,62] . Multiple studies have also shown that concomitant with HCV, HBV, and MTB can directly impact HIV disease progression with excessive T-cell activation in the peripheral blood [40,[63][64][65] . Increased expression of CD38 on both CD4 + and CD8 + T-cells of HIV-TB co-infected subjects has been described relative to HIV mono-infection [63,66,67] .…”

“…Multiple studies have also shown that concomitant with HCV, HBV, and MTB can directly impact HIV disease progression with excessive T-cell activation in the peripheral blood [40,[63][64][65] . Increased expression of CD38 on both CD4 + and CD8 + T-cells of HIV-TB co-infected subjects has been described relative to HIV mono-infection [63,66,67] . This was also consistent with existing evidences that explain the association of HIV/TB co-infection with sustained levels of peripheral activation in immune compartment following pathogenic persistence [67][68][69] .…”