Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic CD4+ T lymphocytopenia (ICL) is a rare heterogeneous disorder defined by CD4+ T-cell counts below 300 cells/muL in the absence of human immunodeficiency virus (HIV) infection or other known immune deficiency disorders. Here, we report the expansion of immature/transitional B cells in patients with ICL, which is associated with elevated serum levels of IL-7. Both the percentage of immature/transitional B cells and levels of IL-7 were inversely correlated with levels of CD4+ T-cell counts and directly correlated to each other. Further analyses of B cells indicated that, in contrast to the activating effects of HIV disease on mature B cells, the expansion of immature/transitional B cells in patients with ICL occurred at the expense of memory B cells. These findings extend previous reports on primary immunodeficiencies as well as HIV disease by suggesting that CD4+ T-cell lymphopenia has an impact on human B-cell development either directly or indirectly via the associated elevation of IL-7 levels.
 ...
PMID:Idiopathic CD4+ T lymphocytopenia is associated with increases in immature/transitional B cells and serum levels of IL-7. 1705 62

Human APOBEC3G (A3G), a deoxycytidine deaminase, is a broadly acting antiretroviral factor expressed in a variety of cells. Mitogen activation of CD4 T cells enhances A3G expression and leads to recruitment of low molecular mass (LMM) A3G, which functions as a post-entry human immunodeficiency virus (HIV) restriction factor, into enzymatically inactive, high molecular mass (HMM) RNA-protein complexes that include Staufen RNA-transporting granules. We now report that interleukin-2 (IL-2), IL-15 and, to a lesser extent, IL-7 enhance the expression of A3G in peripheral blood lymphocytes and that this effect is blocked by inhibitors of the JAK and MAPK signaling pathways. In mixed cultures of CD4+ T cells containing either HMM or LMM A3G, HIV preferentially infected cells containing HMM A3G. A3G shifted into a HMM complex when IL-2, -7, or -15 was added to resting T cells, likely explaining how cytokine treatment renders resting CD4+ T cells permissive to HIV infection. Similarly, poly(I:C)/tumor necrosis factor-alpha-induced maturation of dendritic cells was associated with a sharp increase in A3G expression; however, this induction led to the accumulation of LMM A3G. Together, these results highlight the distinct inductive effects of select cytokines on A3G gene expression and A3G complex assembly that occur in natural cellular targets of HIV infection.
 ...
PMID:Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cells. 1711 Mar 77

Measurements of Bcl-2 and CD25 expression suggested that IL-7R function is modified in CD4 lymphocytes of untreated viraemic patients. The extent of IL-7R function restoration post-HAART was analysed. A positive linear relationship was demonstrated between IL-7Ralpha expression and the magnitude of IL-7-induced responses in healthy individuals, whereas this relationship is lost in HIV-infected patients, suggesting that viraemic patients suffer a receptor signaling transduction defect in IL-7R function. IL-7 responsiveness is only partly restored by HAART.
 ...
PMID:The correlation between levels of IL-7Ralpha expression and responsiveness to IL-7 is lost in CD4 lymphocytes from HIV-infected patients. 1714 74

We analysed the potential influence of hepatitis C virus (HCV) co-infection over IL-7 levels and thymic function in naive HIV-infected patients and after effective HAART. HIV-HCV-co-infected patients had lower plasmatic IL-7 levels compared with HIV-monoinfected patients. This effect may not be associated either with HCV monoinfection or with the rate of liver injury. These lower levels may explain, at least partly, the lower CD4 cell repopulation of HIV-HCV-co-infected patients after HAART.
 ...
PMID:HIV-hepatitis C virus co-infection is associated with decreased plasmatic IL-7 levels. 1719 23

Apoptosis has been suggested as one of the major mechanisms of CD4+ T cell depletion during the course of HIV type 1 (HIV-1) infection. Here, we show that interleukin 7 (IL-7), a nonredundant cytokine that plays essential roles in the generation and homeostasis of the T cell compartment of the immune system, exerts strong antiapoptotic effects ex vivo on both CD4+ and CD8+ T cells derived from HIV-1-infected subjects. The level of IL-7-mediated reduction of apoptosis was inversely correlated with the number of circulating CD4+ T cells, indicating a higher sensitivity to IL-7 effects in patients with more advanced disease. The antiapoptotic effect of IL-7 was uncoupled from the induction of cellular proliferation or endogenous HIV-1 replication. These results provide a further rationale for consideration of IL-7 as an agent of immune reconstitution in HIV-1 infection.
 ...
PMID:Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+ and CD8+ T cells from HIV-1-infected individuals. 1728 97

IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating IL-7 levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection is considered a "natural" model of attenuated HIV disease given its much slower rate of CD4 decline than HIV-1 and limited impact on the survival of the majority of infected adults. We compared untreated HIV-1- and HIV-2-infected patients and found that the HIV-2 cohort demonstrated a delayed increase in IL-7 levels during the progressive depletion of circulating CD4 T cells as well as a dissociation between the acquisition of markers of T cell effector differentiation and the loss of IL-7Ralpha expression. This comparison of two persistent infections associated with progressive CD4 depletion and immune activation demonstrates that a better prognosis is not necessarily associated with higher levels of IL-7. Moreover, the delayed increase in IL-7 coupled with sustained expression of IL-7Ralpha suggests a maximization of available resources in HIV-2. The observation that increased IL-7 levels early in HIV-1 infection were unable to reduce the rate of CD4 loss and the impaired expression of the IL-7Ralpha irrespective of the state of cell differentiation raises concerns regarding the use of IL-7 therapy in HIV-1 infection.
 ...
PMID:Rate of increase in circulating IL-7 and loss of IL-7Ralpha expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyperimmune activation but distinct outcomes. 1731 74

The loss of CD4(+) T cells and the impairment of CD8(+) T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIV(mac251)-infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4(+) or CD8(+) memory T cells, clonal recruitment to the SIV-specific CD8(+) T cell pool, or CD8(+) T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4(+) effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-beta expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals.
 ...
PMID:Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques. 1733 44

IL-7 promotes survival of resting T lymphocytes and induces T cell proliferation in lymphopenic conditions. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We show that IL-7 up-regulates Fas expression on naive and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. IL-7 induced the association of Fas with the cytoskeletal component ezrin and a polarized Fas expression on the cell surface. The potential role of IL-7 in Fas up-regulation in vivo was verified in IL-7-treated macaques and in HIV-infected or chemotherapy treated patients by the correlation between serum IL-7 levels and Fas expression on T cells. IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest an important role for IL-7 in Fas-mediated regulation of T cell homeostasis. Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis.
 ...
PMID:Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection. 1740 19

Serum IL-7 levels correlate with T-cell depletion in HIV-infected individuals. In some patients, we observed that serum IL-7 decreases upon progression to AIDS, suggesting a role for IL-7 in T-cell maintenance in sporadic cases. Interestingly, IL-7 levels were significantly lower in stable long-term non-progressors (LTNP) than in patients who lost the LTNP status in a 3-year follow-up (P < 0.001), indicating that the serum IL-7 concentration might be a valuable marker for maintenance of the LTNP state.
 ...
PMID:Relationship between serum IL-7 concentrations and lymphopenia upon different levels of HIV immune control. 1745 2

We carried out a longitudinal study to analyze the immune recovery of four patients with aggressive HIV-associated lymphoma (HIV+ Ly+) treated with highly active antiretroviral therapy (HAART) and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT). We also studied three control non-HIV-infected patients with lymphoma (HIV-Ly+) and six HIV patients on HAART without lymphoma (HIV+ Ly-). After 12 months of follow-up, the HIV HIV+Ly+ patients reached the pre-ASCT CD4+ levels, despite a transient decrease after the ASCT. All ASCT patients (HIV+Ly+ and HIV-Ly+) showed an increase in CD4+, CD4+ CD45RO+, and CD4+CD28+ T cells/microl. Although HIV+Ly+ patients had values of CD4+, CD4+CD45RO+, and CD4+CD28+ T cells/microl lower than the HIV-Ly+ patients, their recovery rate over the 12 months after ASCT appeared to be better. HIV+Ly+ patients had higher pre-ASCT plasma IL-7 levels than HIV-Ly+, however, these values decreased after ASCT. All ASCT patients showed a slight increase of TCR rearrangement excision circles (TRECs) and they did not have a different pattern of TREC evolution. We could not find differences between HIV+Ly+ patients 12 months after ASCT and HIV+Ly- in DNA-HIV (copies/10(6) cell). Overall, HIV+Ly+ patients showed an appropriate immune reconstitution 12 months after ASCT, and, interestingly, they had an amount of DNA-HIV copies similar to HIV+Ly- control patients in their CD4+ cells.
 ...
PMID:Short communication: Immune reconstitution after autologous peripheral blood stem cell transplantation in HIV-infected patients: might be better than expected? 1750 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>