Comparison of the Frequency of Interleukin (IL)-2-, Interferon-γ-, 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.
- SourceAvailable from: Catarina Cortesao
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- "An equivalent expansion of the CD8 + T-cell subset accompanied by a major reduction of the proportion of naive CD8 + T-cells was also observed in these cohorts (Table 1 and Fig. 1b). ART-Discordants, as previously described for HIV-2+ patients , had a less marked expansion of cells with an intermediate-stage of differentiation, as defined by the expression of CD27 in the absence of CD45RA, than the untreated HIV-1 cohort (Fig. 1b), suggesting, as others have proposed, a failure to fully differentiate CD8 + T-cells in viremic patients . Moreover, the untreated HIV-1 patients also demonstrated a diminished frequency of IL-2 producing CD8 + T-cells that is apparently recovered in ART-Discordants (19.0 ± 3.2% IL-2 + cells within the CD8 subset for ART- Discordants, p = 0.3220, 10.6 ± 1.4% for Untreated HIV-1, p b 0.0001, in comparison with 23.3 ± 2.7% for healthy controls). "
ABSTRACT: A significant proportion of HIV-1+ patients with suppression of viremia under antiretroviral therapy fail to recover CD4(+) T-cell counts (ART-Discordants). Similarly, untreated HIV-2+ patients can also exhibit major CD4 depletion in spite of undetectable viremia. We characterize here the immunological disturbances associated with major CD4-lymphopenia in these two scenarios as compared to untreated viremic HIV-1+ patients with similar CD4-lymphopenia and HIV-1+ patients with successful immunological and virological responses under ART. Low CD4 counts were associated with major naive CD4 and CD8 depletion, irrespective of type of infection or ART-exposure. However, ART-Discordants exhibited lower levels of T-cell activation as compared to both untreated HIV-2 and HIV-1 cohorts, and a less marked increase in circulating IL-7 despite similar CD4 depletion. Nevertheless, ART-Discordants showed a preserved Bcl-2 expression, suggesting increased IL-7 consumption, which in conjunction with the relatively lower T-cell activation may contribute to their CD4 count stability and low rate of opportunistic infections.Clinical Immunology 11/2007; 125(1):67-75. DOI:10.1016/j.clim.2007.07.001 · 3.99 Impact Factor