Close association of CD8⁺/CD38^bright with HIV‐1 replication and complex relationship with CD4⁺ T‐cell count

Abstract

Background: Measuring lymphocyte activation provides information in addition to CD4 1 T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8 1 T-cells. Focusing specifically on CD38 high expression (CD8 1 /CD38 bright ) may be an interesting surrogate gating strategy because CD38 bright characterizes principally activated memory cells.Methods: CD8 1 /CD38 bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4 1 T-cell count.Results: The CD8 1 /CD38 bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8 + /CD38 bright moderately correlated with CD4 + T-cell count independently of the VL (r = 20.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4 + T-cell depletion (median 39% for CD4 + T-cell counts <50/mm 3 ). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals.Conclusions: CD8 1 /CD38 bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. q

Immune Reconstitution During the First Year of Antiretroviral Therapy of HIV-1-Infected Adults in Rural Burkina Faso

“…Both the percentage of marker-positive cells (compared to unstained lymphocytes of each patient) and the median fluorescence intensity (MFI) obtained from FL-2 fluorescence intensity histogram curves of defined subpopulations of cells were assessed. CD38 MFI was measured on CD38 + (instead of total) T-cells in order to focus our analysis on the CD38 bright CD8 + T-cell population [8]. The two subpopulations of CD95 dim and CD95 bright CD4 + T-cells were separately analyzed since we had previously shown that CD95 dim cells essentially correspond to the resting/naïve subpopulation of CD4 + T-cells, whereas CD95 bright cells are of an activated/memory phenotype [6].…”

Long-Term Control of Simian Immunodeficiency Virusmac251 Viremia to Undetectable Levels in Half of Infected Female Rhesus Macaques Nasally Vaccinated with Simian Immunodeficiency Virus DNA/Recombinant Modified Vaccinia Virus Ankara

“…The magnitude of immune activation was investigated by evaluating the fraction of C M and E M CD4 + and CD8 + T cells that expressed high levels of the CD38 marker, a membrane-bound protein with an ADP-ribosyl cyclase function, whose increased expression has been linked with T cell activation (47,48). The analysis was carried out by flow cytometry on PBMCs from week 2 postinfection to time of death (Fig.…”

Pivotal role of HIV and EBV replication in the long-term persistence of monoclonal gammopathy in patients on antiretroviral therapy

“…Polyclonal CD8 1 T-cell hyperactivation is known to be a robust marker of the immune activation driven by HIV and an independent predictive marker of HIV disease progression. 13,14 The persistence of the MG was accompanied by a higher serum immunoglobulin level (P 5 .003) (Figure 1B), mainly restricted to the immunoglobulin G (IgG) isotype. Hypergammaglobulinemia was observed in 11 of 21 patients (52%), namely 8 of 9 (89%) in the persistent MG group and 3 of 12 (25%) in the transient MG group (P , .001).…”