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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The studies have clearly demonstrated that binding sites for opioid peptides, beta-endorphin, and methionine-enkephalin exist on T lymphocytes. beta-Endorphin appears to be immunodepressant, whereas methionine-enkephalin is immunostimulant. Both in vitro and in vivo studies have shown that methionine-enkephalin can influence some immune functions. Since in vitro modification of immune function requires very low concentrations, it is reasonable to believe that methionine-enkephalin plays a physiological role in the immune system. Although not well established, methionine-enkephalin appears to activate T lymphocytes via opioid receptors and triggers a series of intracellular signals leading to the activation of receptors for interleukin-2 (IL-2), OKT10, and active sheep T red blood cell receptors. Methionine-enkephalin enhances the activity of NK cells and induces the production of IL-2, which in turn may recruit and activate other T-cell subsets like CD3 and CD4. Methionine-enkephalin also enhances mitogen-induced proliferation of lymphocytes. Since preliminary studies with methionine-enkephalin in ARC patients have provided beneficial effects by the improvements in their symptoms, it will be worthwhile to extend these observations to a larger number of patients with ARC and AIDS. Finally, it appears that some endogenous opioid peptides and their analogs, in addition to methionine-enkephalin, may provide therapeutic benefits not only in ARC and AIDS but also in other immunodeficient states.
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PMID:Opioid peptides, receptors, and immune function. 217 24

The protective immune response to human immunodeficiency virus type 1 (HIV-1) induced by vaccination will likely include cellular immune responses. We measured lymphoproliferative responses in persons vaccinated with a baculovirus-derived recombinant gp160 candidate AIDS vaccine. Twelve volunteers received either 40 micrograms of rgp160, 80 micrograms of rgp160, hepatitis B vaccine, or alum adjuvant alone on days 0, 30, and 180. Peripheral blood lymphocytes were collected on days 0, 28, 60, 120, 210, and 270 and were cryopreserved. Lymphocyte proliferation to mitogens and rgp160 with and without interleukin-2 stimulation were determined, and lymphokine production and antibody synthesis were measured. All vaccinees responded normally to stimulation with phytohemagglutinin and concanavalin A. One of 3 vaccinees who received 40 micrograms of rgp160, 2 of 2 vaccinees who received 80 micrograms of rgp160, and no controls developed rgp160-specific lymphoproliferative responses. No differences in the production of lymphokines (interleukin-2 and interferon-gamma) after stimulation with mitogens or rgp160 were found when rgp160 vaccinees and controls were compared. We conclude that rgp160 candidate vaccine induces antigen-specific lymphoproliferative responses in humans and does not interfere with immunocompetence as measured by in vitro responses to mitogen stimulation.
AIDS Res Hum Retroviruses 1990 Apr
PMID:Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. 218 3

Immunotherapy, with interleukin-2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection in man have prompted immunotherapeutic studies in the cat. To develop baseline data on hematological responses to infused IL-2, cats were given daily (1-14 days) i.v. injections of 5 x 10(4) U/kg of recombinant human IL-2 (rHulL-2). Complete blood cell (CBC) counts were done weekly. Red blood cell (RBC), neutrophil, and lymphocyte numbers did not change appreciably over the course of the study. In contrast, rHulL-2 caused an eosinophilia in all but the 1 day treatment group. Treatment for 3 days generated a transient eosinophilia on day 7 that returned to baseline by 3 weeks. Five day and 7 day treatments generated an eosinophilia by day 7 that peaked on day 14 and returned to normal values by day 28. Treatment of cats for 14 days did not increase the magnitude or duration of the eosinophilia beyond the 5 or 7 day treatments. Bone marrow (BM) biopsies from rHulL-2-treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3-4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL-2-induced blood eosinophilia. In addition to a maturation signal, rHulL-2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL-2 infusion is discussed.
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PMID:Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo. 223 May 98

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

Since the precise mechanism of host responses to infection with Mycobacterium-avium complex (MAC) is unclear and since cytotoxic lymphocytes may be involved in the destruction of cells infected with intracellular pathogens, we investigated the ability of normal peripheral blood lymphocytes to kill MAC-infected monocytes in a short-term isotope release assay. Nylon wool-passed lymphocytes lysed MAC-infected but not uninfected monocytes during a 4-hr assay. Infected monocytes were less sensitive to cell-mediated killing than the standard natural killer (NK) cell-sensitive cell line K562, although the kinetics of lysis were similar. The release of lymphocyte-derived mediators such as tumor necrosis factor, interleukin-2 (IL-2), and interferon-alpha and -gamma could not be implicated as a cause of monocyte death. Through the use of cell-specific monoclonal antibodies plus complement, the phenotype of the effector cell was that of an NK cell (CD3 negative, partially CD8 negative, and CD16 positive). The use of highly purified, negatively selected NK cells confirmed these results. NK cell-mediated lysis of infected monocytes decreased MAC viability, indicating that this cytotoxic activity would not favor dissemination of the organism. The killing of MAC-infected monocytes was reduced by K562 cells, suggesting that these targets shared common recognition/binding structures. These results suggest that NK-cell function may be important in the prevention of or response to MAC infection and may help explain the predilection of AIDS patients to develop widespread disease.
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PMID:Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes. 231 68

We studied the prevalence of four serum factors in individuals at different stages of human immunodeficiency virus-1 (HIV-1) infection. Soluble interleukin-2 receptors (sIL-2R) were elevated in all antibody-positive groups compared with high-risk, antibody-negative controls. Paraproteins, usually of the IgG-kappa isotype, were found in the sera of a significant number of HIV-1-infected individuals as were antibodies to lymphocytes (ALAs). Serum factors that inhibit proliferation of peripheral blood mononuclear cells from healthy donors appear late in the course of infection and were associated with increasing clinical severity. Measurement of these factors may prove to be useful in defining the stages of infection and in predicting the appearance or exacerbation of symptoms. They may also play a role in the development of the HIV-1-induced immune defects that lead to the expression of clinical acquired immunodeficiency syndrome.
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PMID:Serum factors in the progression of human immunodeficiency virus type 1 infection to AIDS. 235 58

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

Long-term cultures were established of HTLV-III-infected T4 cells from patients with the acquired immune deficiency syndrome (AIDS) and of T4 cells from normal donors after infection of the cells in vitro. By initially reducing the number of cells per milliliter of culture medium it was possible to grow the infected cells for 50 to 60 days. As with uninfected T cells, immunologic activation of the HTLV-III-infected cells with phytohemagglutinin led to patterns of gene expression typical of T-cell differentiation, such as production of interleukin-2 and expression of interleukin-2 receptors, but in the infected cells immunologic activation also led to expression of HTLV-III, which was followed by cell death. The results revealed a cytopathogenic mechanism that may account for T4 cell depletion in AIDS patients and suggest how repeated antigenic stimulation by infectious agents, such as malaria in Africa, or by allogeneic blood or semen, may be important determinants of the latency period in AIDS.
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PMID:Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. 241 2

Immune stimulators such as Corynebacterium parvum (CP) are useful for antitumoral and antiviral therapy. However, the immune trigger cannot be reactivated without adversely affecting the disease. We have tried to amplify the results yielded by a single injection of CP by using either interleukin-2 (IL2) or aspartate salts (ASP). In the present report, we show that IL2 has no detectable clinical effect. In contrast, the addition of an ASP salt increases the antiviral and antitumoral protection afforded by the CP-induced trigger. Moreover, treatment using only ASP slightly protects against tumor development and significantly increases antiviral resistance during experimental encephalomyocarditis (EMC) infection. This ASP-assisted CP immune stimulation improves antitumoral resistance even when ascitic tumors have already developed. In the latter case, tumor regression can even be detected. Since ASP increases T-cell cytotoxicity in vitro and aggravates spontaneous T-cell lymphomas in AKR mice, the involvement of T-cell-mediated immunity may explain antitumoral and antiviral effects. We propose the use of this therapeutic model for human cancer therapy, and possibly for treating AIDS.
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PMID:Aspartate-assisted immune stimulation: its importance in antitumor and antiviral protection. 242 9

A major difficulty limiting the use of immunomodulators in clinical medicine has been the complexity of the immunoregulatory network in which modulation of one component usually perturbs the entire system, thus diminishing the specificity of the approach. Lymphokine-activated killer cells infused with interleukin-2 have proved effective in inducing remissions in several advanced cancers, particularly metastatic renal cell carcinomas. The interferons have shown direct antiproliferative effects as well as specific effects on immune function. Alpha-interferon has shown impressive antitumor effects in hairy cell leukemia and significant antiviral effects in papillomavirus infection of the genital tract. Interleukin-2 has multifaceted effects on various limbs of the inflammatory and immune responses and may be the critical common denominator in the adjuvant effects of several other compounds. Monoclonal antibodies have assumed an increasing role in diagnostic and therapeutic approaches to neoplastic and immune-mediated diseases. Finally, several immunomodulators are currently being tested in the treatment of the immune defect of the acquired immunodeficiency syndrome.
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PMID:NIH conference. Immunomodulators in clinical medicine. 243 78


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