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

Human immunodeficiency virus (HIV) infection causes a number of clinical syndromes and many laboratory abnormalities, often heralding the development of the life-threatening opportunistic infections or malignancies that are known as the acquired immunodeficiency syndrome (AIDS). Drawing heavily on the results of prospective cohort studies, particularly those that my colleagues at the National Cancer Institute and I have conducted, this paper reviews the relationship of AIDS to clinical signs and symptoms, immunologic measures, and viral assays. The risk of AIDS in the next 3 years is at least 25 to 50% for HIV-infected subjects who have oral candidiasis, unexplained fever, unexplained weight loss, a CD4+ lymphocyte count below 200 cells/microliter, or combinations of these. Elevated serum levels of beta 2 microglobulin and neopterin also appear to be strong predictive markers of AIDS, but further work is needed in diverse HIV-infected populations, such as intravenous drug users and persons in pattern II countries, such as Haiti and central Africa. Elevated levels of interferon or HIV-p24 antigen in the serum are insensitive but highly specific AIDS markers that may have predictive value independent of CD4 lymphocyte levels. Several potentially valuable immunologic (immunoglobulin levels, tumor necrosis factor, soluble interleukin 2) and virologic (HIV viremia) assays remain to be thoroughly evaluated or technically simplified. Data from prospective cohort studies have provided clinical and laboratory markers of AIDS risk that have proved essential for therapeutic trials and other clinical decisions. As effective treatments for HIV infection and its complications begin to emerge, these marker data will also prove invaluable for mathematic modeling of the scope, course, and public health response to the epidemic.
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PMID:Prognostic markers for AIDS. 166 94

Systemic lupus erythematosus (SLE) is associated with alterations in immune regulation that results in T cell activation and release of the soluble interleukin 2 receptors (sIL-2R) in serum. SLE, a disease with varied clinical manifestations also has regulatory T cell subset abnormalities in blood. Levels of sIL-2R in serum of patients with active SLE were higher than in those with other common rheumatic diseases. Patients with active SLE and an increased percentage of CD4+ CDw29+ helper inducer (memory) and decreased percentage of CD4+ CD45R+ suppressor inducer (virgin) T cell subsets in blood demonstrated elevated levels of sIL-2R in serum. When compared with clinical manifestations of the disease, the sIL-2R levels in the sera of the patients with active SLE and thrombocytopenia were higher (mean 1710 units/ml) than those in active SLE with nephrotic syndrome (mean 1230 units/ml) or in active SLE with central nervous system disease (mean 1157 units/ml). However, patients with active SLE with humoral immunodeficiency (hypogammaglobulinemia) had highly elevated levels of sIL-2R in serum as compared to other patients with active SLE. The highly elevated levels of sIL-2R in serum may indicate that in vivo T cell activation plays an important role in this disease.
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PMID:Soluble interleukin 2 receptor levels in serum and its relationship to T cell abnormality and clinical manifestations of the disease in patients with systemic lupus erythematosus. 168 Jan 90

Simian immunodeficiency viruses (SIV) are a family of primate lentiviruses similar to human immunodeficiency viruses (HIV) in their genetic sequence and pathogenesis. However, host-derived cofactors which may determine the extent of viral replication are not clearly defined for SIV or HIV infections. A HuT-78 cell line chronically infected with SIV/mac strain 251, was biologically cloned and characterized for the ability to produce infectious viral particles, viral structural protein profile, cellular antigen surface phenotype and tested to determine the effects of recombinant cytokines on SIV replication. Reverse transcriptase (RT) assay was used to measure the replication of SIV/mac in response to various concentrations of recombinant cytokines (1-1000 units/ml). We report that tumor necrosis factor-alpha (rTNF-alpha), gamma-interferon (rIFN-gamma), interleukin 2 (rIL-2), and granulocyte-macrophage colony stimulating factor (rGM-CSF) induced approximately a 2 to 3 fold increase in virus RT activity compared with untreated SIV-infected HuT-78 cells. In contrast, viral replication was not enhanced or minimally enhanced by interleukin 1 (rIL-1), interleukin 3 (rIL-3), or interleukin 4 (rIL-4) at similar dosages. Furthermore, SIV replication in response to rTNF-alpha and rIFN-gamma occurred in a dose dependent fashion. These data suggest that SIV-infected T-lymphocyte lines are responsive to particular cytokines resulting in increased virus production.
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PMID:Cytokine enhancement of simian immunodeficiency virus (SIV/mac) from a chronically infected cloned T-cell line (HuT-78). 172 91

Quantification of human immunodeficiency virus (HIV) proviral DNA in peripheral blood mononuclear cells (PBMC) was performed in 13 HIV-seropositive asymptomatic individuals during 10-24 months by polymerase chain reaction amplification of multiple half-log dilutions of cellular DNA. At enrollment, subjects had a geometric mean titer of 100 copies of HIV provirus per 10(6) PBMC (mean +/- SD, 2 +/- 0.9 log10). In four untreated individuals there was no significant change in provirus levels during a mean period of 13.3 months. In eight patients treated with zidovudine (ZDV) and human recombinant interleukin 2 (rIL-2), HIV provirus copies declined to 13 per 10(6) cells (1.1 +/- 0.8 log10) at the end of the first course of ZDV and rIL-2 at week 20 (p less than 0.01), and to 40 per 10(6) cells (1.6 +/- 0.9 log10) after 12 months of treatment (p less than 0.04). Subsequent courses, which included 12 weeks of ZDV alone or 4 weeks of IL-2 alone, did not significantly change the already depressed provirus copy numbers. Proviral copy number also remained depressed during drug-free "washout periods" between courses. Finally, we observed a return to a geometric mean of 400 copies per 10(6) cells (2.6 +/- 0.3 log10) a mean of 7.9 months after discontinuation of therapy. Measurement of changes in HIV provirus should provide a direct marker for defining antiviral activity of drugs, biologics, and combination therapy.
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PMID:Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration. 173 87

The principal neutralizing domain (PND) for antibody response is located within the V3 variable region of gp120 and can also stimulate T-cell responses. In some adults infected with human immunodeficiency virus (HIV) an HIV-1-specific T-cell response can be detected by demonstrating in vitro proliferation to HIV-1 proteins and peptides. In other HIV-1 infected adults an HIV-1-specific T-cell response can involve interleukin 2 (IL-2) secretion in the absence of T-cell proliferation. To elucidate the T-cell responses to PND in children, we examined the proliferative and the IL-2 secretory responses of peripheral blood lymphocytes from 19 HIV-1-infected children toward a peptide which contained a highly conserved sequence of the principal neutralizing domain of HIVMN (PND-MN). Stimulation with PND-MN induced proliferation of lymphocytes from 2 of the children and IL-2 secretion by lymphocytes from 5 of the children. In a 3-month-old infant, the in vitro cellular response to the PND-MN indicated HIV-1 infection prior to the detection p24 antigen in her serum. Although antibodies directed against PND-MN were detected in all but one of the children examined, the presence of high-affinity/avidity antibodies to the PND-MN correlated with the presence of a cellular response to PND-MN. Thus, in HIV-1-infected children an HIV-1 specific T-cell response in the absence of a proliferative response can be assessed by determination of the IL-2 secretory response and correlates with the generation of high-affinity/avidity antibodies.
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PMID:Cellular and antibody responses directed against the HIV-1 principal neutralizing domain in HIV-1-infected children. 174 76

Vaccinia virus that expressed interleukin 2 (IL 2) was cleared from immunodeficient irradiated mice more efficiently than virus that did not express interleukin 2. These results extend the previously observed protection from nude mice to another model of immunodeficiency. No antibody or cytotoxic T lymphocyte response could be detected in sublethally irradiated mice that had been inoculated with IL 2-expressing vaccinia virus, but levels of splenic natural killer cell activity were elevated. Sublethally irradiated mice that had recovered from IL 2-plus hemagglutinin-expressing vaccinia virus were partially protected against both influenza virus and vaccinia virus. These results indicate that vaccinia virus-expressed IL 2 mediates clearance of primary viral infection via a mechanism that does not involve antibody or cytotoxic T lymphocytes. They also indicate that inclusion of lymphokine genes in live recombinant viral vaccine vectors may increase vaccine safety.
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PMID:Effects of vaccinia virus-expressed interleukin 2 on the immune system of sublethally irradiated mice. 175 76

Two in vitro systems (the DNA synthetic response to mycobacterial antigens and cytotoxicity against lymphoid cells) were used to analyse the effect of thymolymphotropin (TLT) on peripheral blood mononuclear cells (PBMC). Purified protein derivative of mycobacteria (PPD)-driven T-cell proliferation in low-responder donors was increased by the combined treatment with TLT and suboptimal doses of recombinant interleukin 2 (IL-2). Similarly, the activities of natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been enhanced in PBMC cultures pretreated with TLT. Also, TLT showed an enhancing effect on the development of LAK cells capable of lysing Epstein-Barr virus (EBV)-transformed B-lymphocytes infected or uninfected with the human immunodeficiency virus (HIV).
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PMID:The combined treatment of human peripheral blood mononuclear cells with thymolymphotropin and interleukin 2 increases PPD-driven T-cell proliferation and IL-2 induced cellular cytotoxicity against HIV-infected cells. 181 52

A synthetic peptide containing env amino acid (aa) sequence 581 to 597 of the transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1) was tested for its effect on protein kinase C (PKC) and cytoplasmic free Ca2+ [( Ca2+]i) influx-dependent immune functions. We have previously shown that this peptide inhibits PKC-mediated phosphorylation and T-cell receptor-mediated [Ca2+]i influx as well as lymphoproliferation. In this study we demonstrate that the HIV-1 gp41 peptide aa581-597 inhibits lymphoproliferation stimulated via the distinct T-cell-activation molecules CD3, CD2, and CD28, as well as direct stimulation mediated by phorbol ester combined with ionomycin. Further, aa581-597 inhibits both PKC-dependent interleukin 2 (IL 2) production and the [Ca2+]i influx-dependent but PKC-independent induction of IL 2 receptor expression. The HIV-1 gp41 peptide also induces dramatic morphologic changes in lymphocytes, characterized by cytoplasmic ballooning and the acquisition of adherence to plastic, and these changes are dependent on both the length and the temperature of exposure. The results of this study suggest that the HIV-1 gp41 sequence aa581-597 acts at multiple sites to inhibit both PKC activity and [Ca2+]i influx, resulting in the abrogation of several distinct immune functions that are critical for an intact immune response and are defective in HIV-1-infected individuals.
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PMID:A synthetic peptide with sequence identity to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and intracellular calcium influx. 183 84

Healthy, human immunodeficiency virus seronegative (HIV-) volunteers were multiply immunized with a recombinant gp160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40 micrograms or with 80 micrograms (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (Th) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The Th cell functional tests included antigen-induced in vitro interleukin 2 (IL 2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by T cells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV- individuals with rgp160 results in IL 2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances Th function; (c) HIV-specific Th function is up to 100-fold greater in the multiply immunized volunteers than that observed in asymptomatic, HIV-infected individuals; and (d) multiple immunization with rgp160 does not impair Th function to a non-HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger Th cell immunity than does natural infection and suggests that vaccination against HIV may be possible.
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PMID:Immunization with subunit human immunodeficiency virus vaccine generates stronger T helper cell immunity than natural infection. 184 91

A family of structurally related macrocyclic lactones, bryostatins, have recently been shown to display several intriguing pharmacologic properties. Bryostatins are biosynthetic products of bryozoa phyllum of marine animals. To extend the analyses of the biological activities of these highly unusual biosynthetic animal products, we have examined the effect of bryostatin 1 (bryo-1) on the steady-state expression of the human immunodeficiency virus receptor, CD4, by normal peripheral blood T lymphocytes. Incubation of the cells with 5 nM bryo-1 caused a substantial loss of CD4 from the cell surface, as analyzed by flow cytometry using anti-CD4 monoclonal antibody. The modulation of CD4 expression by bryo-1 was not due to a cytotoxicity effect: in the culture conditions where it modulated CD4, bryo-1 also stimulated the expression of the interleukin 2 gene, as indicated by northern blot hybridization. In addition, incubation of the lymphocytes with nanomolar amounts of protein kinase C antagonist, staurosporine, resulted in the inhibition of the bryo-1-induced modulation of CD4 expression. The results of radioimmunoprecipitation analysis of detergent lysates of [35S] methionine-labeled lymphocytes strongly suggest that bryo-1 inhibits the glycosylation and expression of CD4 in a manner similar to that of tunicamycin.
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PMID:Distinct modulatory effects of bryostatin 1 and staurosporine on the biosynthesis and expression of the HIV receptor protein (CD4) by T cells. 186 3


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