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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The T cell-stimulatory cytokine interleukin 2 (IL-2) is being evaluated as a therapeutic in the clinical settings of HIV infection and cancer. However, the clinical utility of IL-2 may be mitigated by its short in vivo half-life, toxic effects, and high production costs. We show here that an IL-2/Ig fusion protein possesses IL-2 immunostimulatory activity in vitro and a long in vivo half-life. IL-2/Ig treatment of healthy rhesus monkeys induced significant increases in CD4(+) T lymphocyte counts and expression of CD25 by these cells. Short courses of IL-2/Ig treatment of simian immunodeficiency virus (SIV)-infected rhesus monkeys in conjunction with antiretroviral drugs resulted in increased CD25 expression on T lymphocytes, and transient increases in CD4(+) T lymphocyte counts. Plasma viremia did not increase in these treated animals. Treatment of healthy or SIV-infected rhesus monkeys with a plasmid encoding the IL-2/Ig protein did not affect CD4(+) T lymphocytes. These results demonstrate that IL-2/Ig has potential utility as an immunostimulatory therapeutic.
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PMID:An IL-2/Ig fusion protein influences CD4+ T lymphocytes in naive and simian immunodeficiency virus-infected Rhesus monkeys. 1146 74

Induction of IL-2 production and increased expression of CD25 were observed in C57BL/10 mice after weekly treatment with gold sodium thiomalate (GST). LP-BM5 murine leukemia virus (MuLV) infected mice treated with GST survived longer, had less cervical lymph node swelling, lower spleen weight, and fewer abnormalities in the expression of the cell surface markers, CD4, CD8a and CD45R/B220 on spleen cells than those that were not treated with GST. Thus, GST treatment may be beneficial through a decrease in disease progression via IL-2 induction in MuLV infected mice. This may have application in human immunodeficiency virus-infected individuals.
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PMID:Immunomodulatory effect of gold sodium thiomalate on murine acquired immunodeficiency syndrome. 1152 62

Heterosexual transmission of human immunodeficiency virus (HIV-1) is the predominant mode of infection world-wide. To better understand sexual transmission of HIV-1 in women we have analysed virus co-receptor and cellular activation marker expression on T lymphocyte subsets from the cervical epithelium and have made comparisons with peripheral blood T cells. Intraepithelial cervical T lymphocytes were obtained with a cytobrush, immunolabelled and analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) were found to be more highly expressed on cervical than on blood T lymphocytes. These higher levels of activation on cervical T lymphocyte subsets could facilitate HIV-1 infection. CXCR4 was expressed at marginally higher levels than CCR5 on T cells from the cervical epithelium and peripheral blood. Thus, the preferential transmission of macrophage tropic strains of HIV-1 following sexual contact cannot be explained solely on the expression of chemokine co-receptors by T lymphocyte subsets.
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PMID:Higher levels of activation markers and chemokine receptors on T lymphocytes in the cervix than peripheral blood of normal healthy women. 1160 Jan 81

Gammadelta T lymphocytes recognize nonpeptidic microbial antigens without MHC restriction and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. This innate recognition involves both T Cell Receptor (TCR) and NK-receptor mediated signalling through non-peptidic metabolites and HLA class I down-regulation. We observed that HLA-masking and nonpeptidic phosphoantigens induce the expression of CD25 and CD69 activation markers on the surface of gammadelta T cells. Interestingly, CD94+ cell depletion by magnetic beads showed that the expression of this antigen is essential for Vdelta2 T cell activation by HLA-masking. Moreover, both phosphoantigen-stimulation and in vitro HIV infection resulted in marked Vgamma9Vdelta2 T cell expansion, whereas HLA-masking was unable to induce proliferative responses. Finally, we observed a relevant hyporesponsiveness to non-peptidic antigens in HIV-infected persons and in cord blood cells from healthy donors when compared to adult PBMC from uninfected donors. Altogether, the reduced ability to naturally recognize the infected cells may contribute to HIV-disease progression and may facilitate maternal transmission of HIV infections.
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PMID:Antiviral activity and anergy of gammadeltaT lymphocytes in cord blood and immuno-compromised host. 1169 34

The macaque-simian immunodeficiency virus (SIV) system is one of the best animal models available to study the role of dendritic cells (DCs) in transmission and pathogenesis of HIV, as well as to test DC-based vaccine and therapeutic strategies. To better define and optimize this system, the responsiveness of macaque monocyte-derived DCs to a variety of maturation stimuli was examined. Characteristic immunophenotypic and functional DC maturation induced by standard monocyte conditioned medium (MCM) was compared to the activation induced by a panel of stimuli including soluble CD40L, LPS, Poly I:C, PGE(2)/TNFalpha, and a cocktail mixture of PGE(2)/TNFalpha/IL-1beta/IL-6. Immunophenotypic analysis confirmed that all stimuli induced stable up-regulation of CD25, CD40, CD80, CD83, CD86, HLA-DR, DC-LAMP (CD208), and DEC-205 (CD205). In general, macaque DCs exhibited weaker responses to LPS and Poly I:C than human DCs, and soluble CD40L stimulation induced variable expression of CD25. Interestingly, while the endocytic capacity of CD40L-matured cells was down-modulated comparably to DCs matured with MCM or the cocktail, the T cell stimulatory activity was not enhanced to the same extent. The particularly reproducible and potent T cell stimulatory capacity of cocktail-treated DCs correlated with a more homogenous mature DC phenotype, consistently high levels of IL-12 production, and better viability upon reculture compared to DCs activated by other stimuli. Furthermore, cocktail-matured DCs efficiently captured and presented inactivated SIV to SIV-primed T cells in vitro. Thus, the cocktail represents a particularly potent and useful stimulus for the generation of efficacious immunostimulatory macaque DCs.
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PMID:Enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of SIV-specific T cell responses. 1179 91

Highly active antiretroviral therapy has succeeded in many cases in suppressing virus production in patients infected with human immunodeficiency virus (HIV); however, once treatment is discontinued, virus replication is rekindled. One reservoir capable of harboring HIV in a latent state and igniting renewed infection once therapy is terminated is a resting T cell. Due to the sparsity of T cells latently infected with HIV in vivo, it has been difficult to study viral and cellular interactions during latency. The SCID-hu (Thy/Liv) mouse model of HIV latency, however, provides high percentages of latently infected cells, allowing a detailed analysis of phenotype. Herein we show that latently infected cells appear phenotypically normal. Following cellular stimulation, the virus completes its life cycle and induces phenotypic changes, such as CD4 and major histocompatibility complex class I down-regulation, in the infected cell. In addition, HIV expression following activation did not correlate with expression of the cellular activation marker CD25. The apparently normal phenotype and lack of HIV expression in latently infected cells could prevent recognition by the immune response and contribute to the long-lived nature of this reservoir.
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PMID:Effect of latent human immunodeficiency virus infection on cell surface phenotype. 1179 62

Highly active antiretroviral therapy has decreased the morbidity and mortality of human immunodeficiency virus (HIV) infection, but latently infected cells remain for prolonged periods. CD4(+) CD45RO(+) T cells are a major latent virus reservoir in HIV-infected persons. Replication-competent, latently HIV-infected T cells can be generated in vitro by infecting peripheral blood mononuclear cells with HIV and then eliminating the HIV-producing cells with an anti-CD25 immunotoxin (IT). The CD25(-) latently infected cells then can be eliminated with an anti-CD45RO IT. This study determined whether this IT also could kill latently infected CD4 T cells from HIV-infected persons with or without detectable plasma viremia. The results show that ex vivo treatment of cells from HIV-positive persons by anti-CD45RO IT reduces the frequency of both productively and latently infected cells. In contrast, CD4(+) CD45RA(+) naive T cells and a proportion of CD4(+) CD45RO(lo) memory T cells are spared.
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PMID:An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons. 1180 12

Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the predominant mode of infection worldwide. Increased risk of HIV-1 transmission has been reported with oral contraceptive use. To elucidate the underlying mechanism of this observation, intraepithelial endocervical T lymphocytes from women using oral contraceptives were analysed for expression of activation and chemokine receptors. T lymphocytes from the cervical epithelium and peripheral blood of women using combined oral contraceptives (COC) and those using no contraceptive method (NONE) were compared. Cervical T lymphocytes were obtained with a cytobrush and in parallel, mononuclear leukocytes were separated from blood by centrifugation over a ficoll-hypaque gradient. Cellular activation markers and HIV-1 chemokine co-receptors, CXCR4 and CCR5, were analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) on T cells were expressed at higher levels in the cervical epithelium than peripheral blood T cells but were no different in those women using COC. CXCR4 was widely expressed on cervical and on blood T cells, but was not influenced by COC use. By contrast, the number of T cells expressing CCR5 increased in women using COC (P<0.05). The level of cervical CCR5 expression per cell was shown to increase on both activated CD4(+) (CD69(+), P<0.05; HLA-DR(+), P<0.01) and CD8(+) (CD69(+), P<0.05; HLA-DR(+), P<0.05) T lymphocytes compared with COC use. These data show that with COC use, the expression of CCR5 on CD4(+) T lymphocytes is increased. Furthermore, the cell surface density of CCR5 is increased on both CD4(+) and CD8(+) T lymphocyte subsets. These findings suggest a mechanism by which oral contraceptive use can increase the risk of HIV-1 transmission.
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PMID:Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women. 1183 99

The high therapeutic efficiency of lymphotoxic purine analogues, pentostatin and cladribine in hairy cell leukaemia which express the antigen CD25 (alpha chain interleukin-2 receptor) suggests the hypothesis whether protracted cellular immunodeficiency after treatment does not represent an important mechanism of control of this specific lymphoproliferation. The authors analyzed a group of 45 patients with CD25-positive hairy cell leukaemia treated with cladribine. In addition to the therapeutic response they evaluated also the state of cellular immunity during the subsequent months and years following cladribine administration. The regression lines of the development of different sub-populations CD4, CD8 and CD56-positive cells, interleukin-2 and its soluble receptor were evaluated separately in patients with persistent remission and patients with growth of the tumourous mass. Although this retrospective analysis provides only limited information we can deduce from it a long-term decline of CD4 lymphocytes correlating with the relatively low incidence of clinical progression of hairy cell leukaemias. The results of this clinical observation are consistent with some reported clinical and experimental observations.
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PMID:[Therapeutic effectiveness of cladribine and cellular immunodeficiency--related effects in hairy-cell leukemia?]. 1206 Dec 4

To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase in the frequency of FAS+ CD8+ lymphocytes was observed following SIVmacJ5 infection only. A transient increase in lymphocytes positive for intracellular IFN-gamma and IL-4 was observed following primary infection with either virus. In contrast, lymphocytes positive for intracellular IL-2 were reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence of detectable superinfection was obtained. Rechallenge of vaccinees did not alter the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles, or generate an anamnestic antibody response. These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge.
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PMID:Mechanisms of protection induced by attenuated simian immunodeficiency virus. 1206 32


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