Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we have examined the relative contributions of CD4+ and CD8+ T cells in controlling an acute or chronic lymphocytic choriomeningitis virus (LCMV) infection. To study acute infection, we used the LCMV Armstrong strain, which is cleared by adult mice in 8 to 10 days, and to analyze chronic infection, we used a panel of lymphocyte-tropic and macrophage-tropic variants of LCMV that persist in adult mice for several months. We show that CD4+ T cells are not necessary for resolving an acute LCMV infection. CD4+ T-cell-depleted mice were capable of generating an LCMV-specific CD8+ cytotoxic T-lymphocyte (CTL) response and eliminated virus with kinetics similar to those for control mice. The CD8+ CTL response was critical for resolving this infection, since beta 2-microglobulin knockout (CD8-deficient) mice were unable to control the LCMV Armstrong infection and became persistently infected. In striking contrast to the acute infection, even a transient depletion of CD4+ T cells profoundly affected the outcome of infection with the macrophage- and lymphocyte-tropic LCMV variants. Adult mice given a single injection of anti-CD4 monoclonal antibody (GK1.5) at the time of virus challenge became lifelong carriers with high levels of virus in most tissues. Unmanipulated adult mice infected with the different LCMV variants contained virus for prolonged periods (> 3 months) but eventually eliminated infection from most tissues, and all of these mice had LCMV-specific CD8+ CTL responses. Although the level of CTL activity was quite low, it was consistently present in all of the chronically infected mice that eventually resolved the infection. These results clearly show that even in the presence of an overwhelming viral infection of the immune system, CD8+ CTL can remain active for long periods and eventually resolve and/or keep the virus infection in check. In contrast, LCMV-specific CTL responses were completely lost in chronically infected CD4-depleted mice. Taken together, these results show that CD4+ T cells are dispensable for short-term acute infection in which CD8+ CTL activity does not need to be sustained for more than 2 weeks. However, under conditions of chronic infection, in which CD8+ CTLs take several months or longer to clear the infection, CD4+ T-cell function is critical. Thus, CD4+ T cells play an important role in sustaining virus-specific CD8+ CTL during chronic LCMV infection. These findings have implications for chronic viral infections in general and may provide a possible explanation for the loss of human immunodeficiency virus-specific CD8+ CTL activity that is seen during the late stages of AIDS, when CD4+ T cells become limiting.
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PMID:CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. 796 95

As part of a continuous search for surrogate markers of therapeutic efficacy in AIDS, spontaneous in vitro production by peripheral blood mononuclear cells of antibody to human immunodeficiency virus type 1 (HIV-1) was investigated in 50 HIV-1-infected adults. It was independent of CD4+ cell counts, p24 antigenemia, serum beta 2-microglobulin concentration, and clinical status of the patients. The effect of zidovudine on this antibody secretion and the appearance of signs or symptoms of HIV-1 disease progression were evaluated in 20 patients over 24 weeks. Anti-HIV-1 antibody secretion decreased significantly (P = .002) as of the first month of zidovudine treatment only in the 13 HIV-1-infected patients without disease progression. This is earlier than the occurrence of variations in CD4+ cell count and serum beta 2-microglobulin concentration. These results suggest that in vitro antibody production could be a surrogate marker for evaluation of the in vivo antiretroviral efficacy of zidovudine, even in p24 antigen-negative patients.
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PMID:Spontaneous in vitro anti-human immunodeficiency virus type 1 antibody secretion by peripheral blood mononuclear cells is related to disease progression in zidovudine-treated adults. 799 75

The objective of this study was to further evaluate the relative safety of extracorporeal photopheresis in the treatment of patients with AIDS-related complex. Twenty patients with AIDS-related complex, three from the initial report and 17 additional patients, were enrolled. The patient population had various risk factors. There were nine homosexuals, five heterosexual consorts of human immunodeficiency virus (HIV)-positive patients, four reformed i.v. drug abusers, and two hemophilia patients. The patients received monthly treatment with extracorporeal photopheresis. In 16 of the 19 patients, this study provides evidence of clinical stability over a longer period. The relative stability of beta 2-microglobulin and neopterin levels demonstrates that photopheresis therapy does not have an untoward effect on the degree of activation of the immune system with respect to induction of HIV replication. Antibody titers to the major viral antigens, envelope glycoproteins (gp) 120 and 41, reverse transcriptase enzyme gp 66/31 and 55, and the core protein p24 remained stable throughout the course of therapy. A subjective improvement was noted in the majority of patients. The evaluation of T-cell subsets revealed that the photopheresis treatment did not have a detrimental effect on CD3 and CD8 cells. Some decreases were noted in the CD4 cell counts but the decline may be less than is normally seen at corresponding stages of HIV infection. Skin test responsivity improved in 11 patients, remained unchanged in seven patients, and declined in two. The preliminary results suggest that in HIV disease, extracorporeal photopheresis is safe and warrants a prospective controlled trial.
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PMID:Extracorporeal photopheresis in the treatment of AIDS-related complex: extended trial. 809 83

A study was performed on 51 human immunodeficiency virus (HIV 1)-infected patients with a previous history of drug abuse. By the CDC staging system for HIV infection they were mainly in advanced stages of that infection, 67% were in IV-A and 8% in IV-C1. Patients were divided in two groups, one composed of 33 individuals who needed AZT therapy and the other of those who did not need that medication (18 patients). Between 3 and 18 months several parameters were assessed on 3 different occasions, according to standard techniques: red blood cells and platelet numeration, CD4 and CD8 cell counts, HIV antigen (p24 Ag), beta 2-microglobulin, high density serum lipoproteins (HDL), and anticardiolipin antibodies (ACA). In the patients treated with AZT the first bioserologic evaluation was performed before starting this therapy. Finally it was observed that p24 AG and ACA were present in 21% of the patients, all of them in advanced stages of HIV infection and under AZT therapy. A significant correlation was only found between CD4 counts and beta 2-microglobulin (R = 0.34; P = 0.0001).
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PMID:[Comparative study of various biological markers in HIV 1 infection]. 809 51

Elevated levels of beta 2-microglobulin and neopterin in cerebrospinal fluid (CSF) have been associated with neurologic complications of infection with the human immunodeficiency virus (HIV). The effect of zidovudine (ZDV) on these markers was assessed by studying the effect of ZDV treatment duration on CSF levels in a cohort of 145 HIV-positive men who were receiving ZDV. CSF beta 2-microglobulin and neopterin levels were significantly lower in those who had been taking ZDV for an intermediate period of time (46-365 days) than in those who had received ZDV either long term (> 365 days) or short term (1-45 days). CSF quinolinic acid levels were independent of duration of ZDV administration. A second CSF evaluation was available after 1 year for 54 HIV-positive men (19 of whom were also in the first cohort) and 11 HIV-negative controls. Patients who had started ZDV between lumbar punctures showed a significant decrease in CSF beta 2-microglobulin, but in those who had been receiving ZDV for > 1 year beta 2-microglobulin increased (p = 0.001). The effect was not observed with neopterin (p = 0.14). (Quinolinic acid levels were not studied longitudinally.) Finally, we observed that CSF levels of beta 2-microglobulin, neopterin, and quinolinic acid correlated strongly with each other in HIV-positive individuals (r = 0.7, p < 0.0001), even though ZDV might have different effects on these markers. In conclusion, we report that initiation of ZDV therapy is associated with a transient decrease in CSF levels of beta 2-microglobulin and neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of antiretroviral therapy on the cerebrospinal fluid of patients seropositive for the human immunodeficiency virus. 810 73

Antibodies against lymphocytes have been shown in human immunodeficiency virus (HIV)-infected patients, but their relevance in the pathogenesis of acquired immune deficiency syndrome (AIDS) remains controversial. We investigated increased levels of lymphocyte surface Ig and antibodies against CD4+ T cells in the plasma. The relationship to CD4 cell depletion and serological parameters were analysed. A three-colour flow cytometric method was used to detect surface Ig on the surface of patients' cells and antibodies in the plasma of the patients. We observed a high percentage of patients with increased surface Ig on CD4+ T cells (94%-47/50). Antibodies in the plasma reacting with healthy donors' CD4+ T cells were detectable in 72% (23/32) of the patients. CD4 cell-surface Ig correlated well with surface Ig on different T-cell subpopulations but not with increased surface Ig on B cells. Only one control showed elevated surface Ig, plasma antibodies against lymphocytes were not detectable. Surface Ig levels of CD4+ T cells were closely associated with the CD4 cell number in HIV-infected patients of all stages of disease (r = -0.67, P = 0.00005). Other lymphocyte subsets' surface Ig did not show a significant association to CD4 cell depletion. Surface Ig and antibodies against CD4+ T cells were not related to levels of beta 2-microglobulin, p24 antibodies or interleukin-6 (IL-6), and did not depend on hypergammaglobulinaemia. In conclusion surface Ig on CD4+ T cells is likely to have an autoantibody origin. The high prevalence and association to CD4 depletion support the view that autoimmune phenomena could be involved in the pathogenesis of AIDS.
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PMID:Relationship of antibodies against CD4+ T cells in HIV-infected patients to markers of activation and progression: autoantibodies are closely associated with CD4 cell depletion. 810 20

Cytopathic mechanisms in human immunodeficiency virus type 1 (HIV-1) infection involve syncytia formation, and it appears likely that increased expression of intracellular adhesion molecule 1 (ICAM-1) is involved in these cell adhesion phenomena. In this study, we determined serum concentrations of soluble ICAM-1 (sICAM-1) in 27 patients with HIV-1 infection and a control group. In addition, we compared sICAM-1 values to CD4+ T-cell counts, serum beta 2-microglobulin (beta 2M) and serum neopterin levels. HIV-1-infected patients had significantly higher sICAM-1, beta 2M and neopterin levels than controls. The subgroup of patients with Walter-Reed stages 3-6 had only slightly higher sICAM-1 concentrations in serum than Walter-Reed stages 1-2. The sICAM-1 concentrations in HIV-1-seropositive patients correlated with beta 2M levels but neither with neopterin nor with CD4+ T-cell counts. Increased sICAM-1 may result from immune activation, which enhances the expression of ICAM-1 in patients with HIV-1 infection.
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PMID:Increased levels of serum intercellular adhesion molecule 1 in HIV infection are related to immune activation. 810 76

Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression.
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PMID:Markers predicting progression of human immunodeficiency virus-related disease. 811 88

A tumour-associated antigen known as 90K has been found in high concentrations in the serum of patients infected with human immunodeficiency virus (HIV) even in the absence of neoplastic complications. In order to investigate the relationship between the production of 90K and soluble inflammatory mediators, we studied serum concentrations of the antigen, tumour necrosis factor-alpha (TNF-alpha), interleukin-I-alpha (IL-I-alpha), interferon-gamma (IFN-gamma), IFN-alpha, neopterin and beta 2-microglobulin (beta 2-m) in patients with non-neoplastic HIV infection at various stages of disease and in control persons. The antigen was detected in all those studied but its concentration was higher in HIV-infected patients compared with controls (P < 0.001), increasing progressively with advancing stages of disease. There was a negative correlation between concentrations of 90K and IL-I-alpha in patients in U.S.A. Centers for Disease Control groups II and III (P < 0.02) and also between that of 90K and both TNF-alpha (P < 0.01) and IL-I-alpha (P < 0.05) in control persons. The results indicate that 90K is not merely a tumour-associated antigen and that its production may be part of immune and inflammatory responses in the absence of neoplasia. The correlation between the concentrations of 90K and of some cytokines in asymptomatic patients and healthy persons suggests that 90K may be part of a network of immune and inflammatory reactants.
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PMID:Relationship between the tumour-associated antigen 90K and cytokines in the circulation of persons infected with human immunodeficiency virus. 816 31

Forty-three human immunodeficiency virus-infected patients with Pneumocystis carinii pneumonia (PCP) were enrolled in a study of adjunctive corticosteroid treatment for 10 days versus placebo, in addition to antimicrobial treatment. Levels of neopterin and beta 2-microglobulin (beta 2M) were determined in consecutive serum samples. Initiation of antimicrobial treatment resulted in significantly increased neopterin levels, whereas beta 2M levels slightly decreased from pretreatment levels. In patients treated with corticosteroid, both neopterin and beta 2M decreased, by approximately 50% and approximately 30%, respectively, and returned to baseline after discontinuation of corticosteroid treatment. Antimicrobial treatment alone did not affect either neopterin or beta 2M in healthy controls. Results indicate that treatment has a differential effect on the immune response: increased macrophage activation leading to neopterin production and decreased production of beta 2M by lymphocytes. Further, addition of corticosteroids modified and decreased this immune activation and may explain the earlier demonstrated beneficial effect of corticosteroids in PCP treatment.
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PMID:Differential effect on serum neopterin and serum beta 2-microglobulin is induced by treatment in Pneumocystis carinii pneumonia. 816 17


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