Comparison of the frequency of interleukin (IL)-2-, interferon-gamma-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes.
ABSTRACT Human immunodeficiency virus (HIV) type 2 infection is associated with a better clinical outcome, slower rates of CD4 T cell decline, and lower viremia than is HIV-1. This study compares HIV-1 and HIV-2 in regard to the percentages of interleukin (IL)-2-, interferon (IFN)-gamma-, and IL-4-producing cells at the single-cell level, as determined by flow cytometry. At a given degree of CD4 T cell depletion, the frequency of T cells able to produce IL-2 is better preserved in HIV-2 than in HIV-1 infection, particularly within the CD4 T cell subset. As described for HIV-1 immunodeficiency, HIV-2-positive patients exhibit a marked expansion of terminally differentiated effector CD8 T cells (CD28(-)CD27(-)IFN-gamma(+)). However, the proportion of CD8 T cells able to simultaneously produce IL-2 and IFN-gamma is higher in HIV-2 disease. Considering the central role of IL-2 as a lymphocyte proliferative and survival factor, these findings provide a possible immunologic basis for the distinct course of HIV-2 immunodeficiency.
- AIDS (London, England) 04/2014; 28(7):1075-7. · 4.91 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background. Interleukin (IL)-22 is emerging as a key cytokine for gut epithelial homeostasis and mucosal repair. Gut disruption is a hallmark of HIV infection. Here we investigated IL-22 production and gut mucosal integrity in HIV-1-infected individuals receiving long-term antiretroviral therapy (ART).Methods. Biopsies from 37 individuals performing colonoscopy primarily for cancer screening, 17 HIV-1-infected and 20 healthy age-matched controls, were assessed.Results. We found significant depletion of sigmoid IL-22-producing CD4 T-cells (Th22) even after prolonged ART, contrasting with the apparently normal compartments of regulatory and IL-17-producing, as well as total mucosal CD4 T-cells. Despite the preferential Th22 depletion, IL-22-production by innate lymphoid cells (ILC) was similar to that observed in seronegatives, and transcription of molecules relevant for IL-22 production was preserved (AHR, IL23, IL23R, IL1B, IL6, and TGFB1). Remarkably, transcripts of IL-22 target genes (REG3G, DEFB4A, S100A9, MUC1, MUC13) were unaltered, suggesting an adequate production of antimicrobial peptides and mucins. In agreement, enteric epithelial architecture was fully preserved.Conclusion. Despite the reduced Th22 subset, innate IL-22-mediated mechanisms, essential for sigmoid mucosa integrity, were fully operational in long-term treated HIV-1-infected individuals. Our data highlight IL-22-production by ILC as an important target for therapies aimed at facilitating human mucosal reconstitution.The Journal of Infectious Diseases 03/2014; · 5.85 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Despite the strong correlation of T-cell CD38 expression with HIV disease progression, evidence linking CD38 expression and dysfunction at the single cell level is scant. Since CD38 memory CD4 T cells, especially those from HIV-infected persons, fail to induce CD154 (CD40L) while responding to a superantigen with interferon (IFN)-γ or interleukin (IL)-2, we aimed to determine if recall responses to cytomegalovirus (CMV) were similarly affected in the CD38 memory CD4 T-cell subpopulation. Peripheral blood mononuclear cells from HIV+ patients and healthy controls were incubated 14 h with CMV antigens, the superantigen Staphylococcus aureus enterotoxin B or medium, and labeled for identification of central memory (TCM) and effector memory (TEM) CD4 T cells, and for the intracellular detection of induced CD154, IFN-γ and/or IL-2 by flow cytometry. Compared with CD38 cells, CD38 TCM cells from patients had less CD40L induction after CMV stimulation, and increased IFN-γ response. Patients' CD38 TEM cells showed a lower IL-2 response, and tended to have a greater IFN-γ response, in which CD154 induction frequently failed. CMV-specific responses of patients' CD38 TCM and TEM cells were dominated by IFN-γ, and almost all IL-2 cells co-expressed IFN-γ. IL-2 responses to the polyclonal activator S. aureus enterotoxin B were also significantly less frequent among CD38 TCM and TEM cells than in CD38 cells. Patients' CD38 memory CD4 T-cell responses to CMV favor the effector cytokine IFN-γ over IL-2, in the context of deficient CD154 induction, which may limit co-stimulation, proliferation and survival.AIDS (London, England) 01/2014; 28(3):311-6. · 4.91 Impact Factor