Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to the T cell mitogen Phytohemagglutinin-P (PHA-P) in a dose-dependent fashion. This inhibition was mediated via the H2 receptor since cimetidine, a known H2 antagonist, removed the inhibition, whereas the addition of the H1 antagonist Diphenhydramine did not. Inhibition occurred during the inductive phase of the cell cycle, since histamine added 24 hours after PHA-P stimulation had no effect on subsequent T cell proliferation, and was attributable to inhibition of interleukin-2 (IL-2) gene expression. Both secreted IL-2 and messenger RNA coding for IL-2 were inhibited by histamine. In contrast, histamine exerted no inhibitory effect on the expression of cell surface receptors for IL-2 as determined by flow cytometry. Furthermore, histamine-treated cells retained full responsiveness to exogenously administered IL-2, which completely reversed the anti-proliferative effect of histamine. In some donors, histamine enhanced the percentage of IL-2 receptor positive cells. Stimulated PBMC from AIDS KS patients as a group, displayed a lower percentage of IL-2 receptor bearing cells, which was significantly increased by the addition of histamine even at concentrations as low as 10(-6) M and peaking at 10(-3) M. These findings indicate that histamine exerts its anti-proliferative effects on T cells by inhibiting IL-2 production, via blockade of IL-2 gene expression. In addition, histamine seems to exert immunomodulating effects on IL-2 receptor expression, particularly in those individuals with AIDS-KS.
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PMID:Histamine blocks interleukin 2 (IL-2) gene expression and regulates IL-2 receptor expression. 226 28

To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the alpha/beta T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2. 238 2

Immunomodulative actions of isoprinosine were tested in 100 prodromal homosexual males and 23 patients who have been diagnosed with AIDS. All subjects showed reduced T helper cells although T suppressor cell counts were normal. Proliferative responses, particularly T cell-dependent B cell function, were severely impaired in prodromal and AIDS subjects. Upon co-cultivation of their lymphocytes with isoprinosine, significant upward modulation, and in some cases, normalization, of lymphocyte functions as monitored by PHA- and PWM-induced blastogenesis was achieved in prodromal subjects. Similar degrees of modulation but not normalization of lymphocyte functions were observed in patients with severe symptoms of AIDS.
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PMID:Immunopotentiation of impaired lymphocyte functions in vitro by isoprinosine in prodromal subjects and AIDS patients. 241 72

Alloantigen specific primary cytotoxic T lymphocyte (CTL) responses were examined in vitro in 10 patients with AIDS and nine with AIDS-related complex (ARC). The lymphocytes from patients with AIDS and ARC expressed significantly less (P less than 0.01) CTL activity (mean +/- s.d.; 4.7 +/- 9% and 10 +/- 11% respectively) when compared with CTL activity in normal healthy heterosexual controls (28 +/- 9.5%). When data were analysed for individual patients, lymphocytes from nine of 10 patients with AIDS and six of nine with ARC had deficient or no CTL activity. In vitro addition of purified human interleukin-2 (IL-2) during the generation of CTL resulted in significant enhancement (P less than 0.05) of CTL activity in ARC group (mean +/- s.d.; 27 +/- 18) but not in AIDS group (mean +/- s.d.; 8 +/- 8%). The presence of IL-2 augmented the induction of CTL activity in three of nine patients in AIDS group and in five of six in ARC group. In vitro addition of lectin-free supernatant (SN) obtained from cultures stimulated with PHA as well as with lymphoid cell restored the CTL functions in three of six AIDS patients and in one patient with ARC who did not respond to exogenous IL-2. The CTL activity developed in the presence of SN was higher than that manifested in the presence of IL-2 in both AIDS (SN versus IL-2; mean +/- s.d., 18 +/- 15.6% versus 8 +/- 8%) and in the ARC group (SN versus IL-2; mean +/- s.d., 35 +/- 13.9% versus 27 +/- 18.3%). Lymphocytes from three AIDS patients, however, failed to develop any CTL activity in the presence of either IL-2 or SN. These results demonstrate that: (i) the lymphocytes from majority of patients with AIDS and with ARC have deficient ability to develop into alloantigen specific primary CTL effectors, and (ii) the defective CTL functions are restored by the addition of purified IL-2 or SN in all patients with ARC and only in a subset of patients with AIDS, suggesting heterogeneity of pre-CTL to respond to IL-2 and some differentiation factor in order to differentiate in CTL effectors.
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PMID:Antigen-specific primary cytotoxic T lymphocyte (CTL) responses in acquired immune deficiency syndrome (AIDS) and AIDS-related complexes (ARC). 241 63

Immunological and mycological investigations were carried out in 21 Swedish homosexual males. One of them had AIDS, one pre-AIDS and 19 lymphadenopathy of whom 18 fulfilled the criteria of persistent generalized lymphadenopathy (PGL) as defined by the Centers for Disease Control, Atlanta, (CDC). The patients were investigated immunologically with respect to their in vitro lymphocyte reactivity to various mitogens. The patients with AIDS and pre-AIDS belonged to the group of 8 patients with low response to mitogens. Blood helper T cell percentages and serum beta 2-microglobulin concentrations correlated with the PHA reactivity. Three patients, with the diagnoses AIDS, pre-AIDS and PGL respectively, had clinical signs of oral candidiasis with rich growth of Candida albicans in culture. These were all low responders to mitogen stimulation. Six cases of tinea pedis were diagnosed and seemed to be distributed among the patients irrespectively of the severity of their immunological disorders.
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PMID:Persistent generalized lymphadenopathy: immunological and mycological investigations. 242 Jan 16

Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated.
AIDS Res 1986
PMID:Partial plasma exchange in patients with AIDS and Kaposi's sarcoma. Plasmapheresis in AIDS. 242 82

Functional and phenotypical parameters demonstrated significant aberrations in both prodromal males and patients with the acquired immune deficiency syndrome (AIDS). Impaired B-cell functions as quantitated by Staphylococcus aureas Cowan Strain I (SAC) and pokeweed mitogen (PWM)-induced blastogenesis, intracytoplasmic immunoglobulins and spontaneous immunoglobulin were associated with a significant decrease in Leu3+ cells but unrelated to Leu2+ lymphocytes. The functional subsets of the latter were further defined by monoclonal antibodies (Leu8 and HLA-DR) applying dual color flow cytometry. Activated and effector-suppressor subsets with the phenotypes Leu2+ HLA-DR+ and Leu2+ Leu8- were elevated while both subsets of helper and suppressor-inducing helper lymphocytes, Leu3+ Leu8- and Leu3+ Leu8+, were depressed. These data demonstrated a broad spectrum of dysfunction involving all 3 stages of B-cell development in AIDS as well as possible defects in the feedback suppressor loop which regulates both the helper and suppressor T-lymphocyte system and B-cell functions. While in vitro incubation with isoprinosine had no modulative effect on SAC-induced blastogenesis (resting B-cell activities), it did modulate both PHA, PWM-induced transformation and the spontaneous secretion of immunoglobulins (partially and fully activated B-cell activities). In co-incubation with PWM, isoprinosine augmented the expression of inducer cells for helper functions while enhancing to normal level the number of suppressor-inducing helper cells. In addition, it reduced activated and effector-suppressor cells to near normal range in the PBL of high risk homosexuals. Only marginal modulation, however, was observed in suppressor subsets of AIDS subjects. This interference with the defective feedback loop may account for the selective clinical and immunoregulatory actions of this drug.
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PMID:Restoration of impaired B- and T-lymphocyte subsets and functions in vitro by isoprinosine in prodromal homosexuals and AIDS patients. 242 80

We have studied whether the decreased lymphocyte proliferative responses of AIDS lymphocytes to stimulation by mitogens and antigens may be overcome when challenged with a combination of calcium ionophore A23187 and phorbol ester PMA. Comparison of the proliferative response of lymphocytes from nine patients with AIDS with the response of lymphocytes from nine control subjects showed that the response of AIDS lymphocytes was severely decreased when stimulated with PHA and no further response could be achieved by stimulation with A23187/PMA. On the other hand, no significant difference between the PHA-induced rise of cytoplasmic free calcium concentration ([Ca2+]1) in normal and AIDS lymphocytes was observed. The percentage of cells expressing IL-2 receptors (CD25) was also normal both after addition of PHA and after addition of A23187/PMA and the expression was normal on both CD4 and CD8 cells. The production of IL-2 in normal lymphocytes stimulated with A23187/PMA was 33 times higher than that after stimulation with PHA. In AIDS lymphocytes the production of IL-2 induced by all activators was severely decreased compared to control subjects, although the production of IL-2 after stimulation with A23187/PMA was higher than that in control lymphocytes after stimulation with PHA. The present study shows that a direct activation of protein kinase C combined with mobilization of cytoplasmic calcium does not overcome the lymphocyte proliferative deficiency of AIDS lymphocytes.
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PMID:Stimulation of AIDS lymphocytes with calcium ionophore (A23187) and phorbol ester (PMA): studies of cytoplasmic free Ca, IL-2 receptor expression, IL-2 production, and proliferation. 249 38

Twelve patients with the acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma were treated with recombinant human gamma-interferon (rIFN-gamma). A rapid, substantial increase in the fraction of HLA-DQ-positive monocytes was noted after treatment with rIFN-gamma. The rIFN-gamma-induced increase in monocyte HLA-DQ was seen throughout the course of treatment, with the percentage of HLA-DQ-positive monocytes dropping slightly following each week's treatment with rIFN-gamma and then rapidly increasing following the next course of treatment. Although the percentage of HLA-DR-positive monocytes was unchanged (HLA-DR was expressed on greater than 80% of monocytes prior to treatment), the density of HLA-DR on monocytes also increased following rIFN-gamma treatment. Following rIFN-gamma treatment, no changes were seen in CD3, CD4, CD8 T cell numbers, in T cell subset ratio (CD4/CD8), in Leu 7 or CD16 (Leu 11) cell number, in spontaneous Ig secretion, in PHA-induced in vitro proliferation, or in NK activity. These results indicate that exposure to rIFN-gamma in vivo led to the increased expression of class II antigens on monocytes in patients with AIDS.
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PMID:Gamma-interferon-induced monocyte major histocompatibility complex class II antigen expression individuals with acquired immune deficiency syndrome. 250 69

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.
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PMID:HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway. 256 29


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