Tsunemi S, Iwasaki T, Imado T et al.Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients. Aids 19:879-886

Division of Thrombosis and Hemostasis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
AIDS (Impact Factor: 5.55). 06/2005; 19(9):879-86. DOI: 10.1097/01.aids.0000171401.23243.56
Source: PubMed


To determine whether the frequencies of CD4+CD25+ regulatory T cells (T Reg) were related to immune status in HIV-infected patients.
Peripheral blood CD4 T-cell populations were examined for T-helper 1 cells (Th1), T-helper 2 cells (Th2), and T Reg by intracellular staining for interferon (IFN)-gamma and interleukin (IL)-4, and surface staining for CD25, respectively. The immunoregulatory properties of T Reg were assessed by measurement of the inhibitory effects of isolated CD4+CD25+ T Reg on CD4+CD25- T-cell proliferation.
Isolated CD4+CD25+ T Reg from both HIV-infected patients and healthy controls strongly expressed CD45RO, HLA-DR, and FoxP3. HIV-infected patients with detectable plasma HIV-1 RNA showed a statistically significant increase in CD4+CD25high T Reg frequencies (P < 0.05) compared to healthy controls, with T Reg frequency inversely proportional to CD4 T-cell count (P < 0.01). However, in HIV-infected patients with undetectable plasma HIV-1 RNA, CD4+CD25high T Reg frequencies were not increased and were not related to CD4 T-cell counts. In both HIV-infected patient groups, T Reg frequency was inversely related to Th1 frequency (detectable HIV-1 RNA: P < 0.05; undetectable: P < 0.001), but positively related to Th2 frequency (detectable HIV-1 RNA: P < 0.01; undetectable: P < 0.001). T Reg activity was lower in patients with detectable plasma HIV-1 RNA than in patients with undetectable plasma HIV-1 RNA.
Increased T Reg frequencies in peripheral blood were related to low peripheral blood CD4 T-cell counts and polarization toward Th2 immune responses in HIV-infected patients.

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    • "Regulatory T-cells (Tregs) are an important cell population that maintains central tolerance as well as controls the overall response to the invading pathogens, including viruses, however, their role during HIV infection remains controversial. The natural immune-suppressive ability of Tregs may be playing dual role during HIV infection, being harmful to the host for suppressing the viral- specific immune response [2], [3], [4], [5] on one hand and being beneficial at the same time for suppressing the hyperimmune activation state characteristic of this disease [6], [7], [8], [9]. In order to ascertain their behavior in a co-infected host and also if Mtb has any modulatory effect on Tregs that may change the course of HIV infection in the co-infected host, we have investigate the role of Tregs during HIV infection alone or during Mtb co-infection. "
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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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    • "In addition, it has been demonstrated that these immununosuppressive cells play a role in chronic infection by microbial pathogens such as hepatitis B virus, HIV, leishmania, Helicobacter pylori etc. [26] [27] [28]. Among the different clinical manifestations of tuberculosis, pulmonary tuberculosis (PTB) and tuberculous pleurisy (TP) are frequent presentations. "
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    ABSTRACT: Background CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) play a fundamental role in the control of immune responses by down-regulating the function of effector CD4+ or CD8+ T cells. Active suppression by Treg might be important in controlling immune responses against Mycobacterium tuberculosis (Mtb). This study was conducted to evaluate the cellular immune response to Mtb, by evaluation of Treg cells in peripheral blood mononuclear cells (PBMCs) from patients with active pulmonary tuberculosis (PTB), patients with tuberculous pleurisy (TP) and healthy positive PPD persons as control, then evaluation after 6 months of anti-TB therapy, also evaluation of Treg cells in pleural fluid mononuclear cells (PFMCs) from patients with tuberculous pleurisy (TP). We compared the frequency of CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in 20 patients with active pulmonary TB (PTB), 15 tuberculous pleurisy (TP) and 20 control latent tuberculosis. Results Treg frequencies in peripheral blood were significantly higher in patients with PTB and TP than in the control group (p < 0.001). Treg frequencies were significantly higher in pleural effusions than in peripheral blood in the same group (p < 0.001). Treg frequencies in peripheral blood were significantly decreased after 6 months of anti-TB treatment (p < 0.001). Objectives Immune regulatory mechanisms may limit the immunopathologic condition of infection with M. tuberculosis and suppress cellular immune responses in the host. We investigated the CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in patients with pulmonary tuberculosis, tuberculous pleurisy and latent TB, and the frequencies of CD4+CD25+FoxP3+ T-cells after anti-TB therapy. Conclusion MTB infection is associated with an increase in the frequency of CD4+CD25+FoxP3+ Treg in the blood of PTB and TP, in the pleural fluid of TP, decrease in the frequency after anti-TB therapy.
    01/2013; 63(1). DOI:10.1016/j.ejcdt.2013.10.013
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    • "On the contrary, the authors also found a positive correlation for the Th2 cytokine IL-4. A positive correlation has also been reported between a Th2 cytokine profile and a higher frequency of T reg while a Th1 profile showed a negative correlation [15]. HIV-specific Th1 cells may play a major role in the contention of the virus and progression to AIDS. "
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    ABSTRACT: In chronic HIV infection a progressive Th1 to Th2/Th0 cytokine-profile shift is related to disease progression. One of the possible benefits of a therapeutic vaccination might be to counterbalance this phenomenon to allow viral replication control under a Th1-type immune response. TERAVAC-HIV-1 is a multiantigenic formulation vaccine candidate against HIV-1 which comprises the recombinant protein CR3 that contains T cell epitopes and the surface and nucleocapsid antigens of Hepatitis B Virus (HBV). Previous studies showed that such virus like particles of the HBV provide a Th1 adjuvant effect. The present studies examined the capacity of TERAVAC to elicit a Th1 response in the presence of an ongoing HIV-specific Th2-type response in Balb/c mice. To examine this issue, we injected subcutaneously the animals with CR3 or viral lysate in alum which resulted in a Th2-type response. The CR3-specific Th2-type response was verified by induction of IL-4 and IL-10 secretion in ex vivo stimulated splenocytes without secretion of IFN-γ and IgG2a antibodies in serum. Further subcutaneous and simultaneous subcutaneous-nasal immunizations of the same mice with TERAVAC promoted IFN-γ secretion and production of IgG2a antibodies in accordance with a Th1-type response. This result suggests a therapeutic benefit of this vaccine candidate in the restoration of the Th1-type HIV-specific cellular response in seropositive patients.
    Immunology letters 11/2012; 149(1-2). DOI:10.1016/j.imlet.2012.11.007 · 2.51 Impact Factor
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