FOXP3 mRNA levels are decreased in peripheral blood CD4(+) lymphocytes from HIV-positive patients

Laboratoire d'Immunogénétique Moléculaire, Faculté de Médecine de Rangueil, Toulouse, France.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2005; 39(4):381-5. DOI: 10.1097/01.qai.0000169662.30783.2d
Source: PubMed


The impact of HIV infection on regulatory CD4(+)CD25(high) (Treg) lymphocyte subpopulations was evaluated by FOXP3 quantitative reverse transcriptase polymerase chain reaction and by flow cytometry. FOXP3 mRNA was quantified in peripheral blood mononuclear cells or purified CD4(+) lymphocytes from HIV(+) lymphopenic patients. Patients were distributed among clinical stages A, B, and C and received highly active antiretroviral therapy. The frequency of CD4(+)CD25(high) lymphocytes, measured by flow cytometry, was decreased in HIV patients (n = 38) compared with the group of uninfected subjects (n = 39). FOXP3 mRNA levels were found decreased in HIV patients (n = 25) compared with controls (n = 17) when expression of CD3gamma or beta-actin but not that of TATA box binding protein 1 was used for data normalization. Our results are compatible with a decrease of the Treg lymphocytes during HIV infection. The consequences of a Treg decrease are discussed in the context of immunologic anomalies observed during HIV infection.

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    • "The role and frequency of Tregs in HIV-1 infected individuals have long been controversial. Some studies suggest that Tregs get depleted by HIV infection [13], [14], [15], while others indicate that the proportion of these cells may be rather increased [9], [16]. This difference in opinion could be due to differences in the stage of the disease at the time of sampling by the researchers or infection with different HIV-1 strains. "
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    ABSTRACT: Understanding of the chronic immune activation, breakdown of immune defense and synergistic effect between HIV and Mycobacterium tuberculosis (Mtb) may provide essential information regarding key factors involved in the pathogenesis of HIV disease. In this study, we aimed to highlight a few of the immunological events that may influence and accelerate the progression of HIV disease in the presence of co-infecting Mtb. A cross-sectional study was performed on cohorts, including anti-tubercular therapy (ATT) naïve active pulmonary tuberculosis (PTB) patients, antiretroviral therapy (ART) naïve HIV-1 infected individuals at different stages of disease, ATT and ART naïve HIV-PTB co-infected individuals and healthy controls. A significantly higher T-regulatory cell (Treg) frequency coupled with the high FoxP3 expression in the CD4 T-cells indicated an immunosuppressive environment in the advance stage of HIV-1 infection. This is further substantiated by high HO-1 expression favoring TB co-infection. Functionally, this change in Treg frequency in HIV-1 infected individuals correlated well with suppression of T-cell proliferation. Mtb infection seems to facilitate the expansion of the Treg pool along with increased expression of FoxP3, specifically the variant-1, as evident from the data in HIV-1 co-infected as well as in patients with only PTB. A significantly lower expression of HO-1 in co-infected individuals compared to patients with only HIV-infection having comparable CD4 count correlated well with increased expression of CCR5 and CxCR4 as well as NF-κB and inflammatory cytokines IL-6 and TNF-α, which collectively may contribute to enhanced viral replication and increased cell death, hence faster disease progression in co-infected individuals.
    PLoS ONE 09/2014; 9(9):e106815. DOI:10.1371/journal.pone.0106815 · 3.23 Impact Factor
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    • "Although no difference was observed in the frequency of these Treg cells in young individuals, infected or not, a dramatic loss of these cells associated with elevated frequency of Env-specific IL- 10-producing CD4 + FoxP3 − CD152 + T cells was observed in the peripheral blood of aged AIDS patients. Some studies have demonstrated that Tregs decreased in patients with chronic HIV infection [29] [30] [31] [32] and in rhesus macaques experimentally infected with SIV [33]. Direct infection and killing have been proposed as possible causes of the decrease in number of these cells [27]. "
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    ABSTRACT: This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1β by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.
    Clinical Immunology 08/2012; 145(1):31-43. DOI:10.1016/j.clim.2012.08.002 · 3.67 Impact Factor
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    • "Tregs are major producers of transforming growth factor, (TGF-)  α, which promotes tissue fibrosis and limits immune reconstitution [59]. In direct contrast, however, other studies have reported decreased levels of Tregs in HIV-infected individuals [60], and in one study, depletion of Tregs in HIV infection was found to be associated with immune activation [61]. "
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    ABSTRACT: Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies.
    Advances in Virology 06/2012; 2012:434036. DOI:10.1155/2012/434036
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