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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (M phi) are only effective in stimulating memory responses. Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked. Here comparisons between DC and M phi in stimulating secondary T-cell responses in HIV infection were made. Adherent M phi, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [3H]thymidine in 20 microliters hanging drop cultures. DC, but not M phi, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, M phi from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not M phi function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells may be cumulative; failure of secondary activation (e.g. by M phi) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches.
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PMID:Antigen-presentation by macrophages but not by dendritic cells in human immunodeficiency virus (HIV) infection. 153 9

Eleven (nine CD4+ and two CD8+) protein purified derivative-specific and eight tetanus toxoid-specific T cell clones (TCC), established from the peripheral blood of healthy persons, were cocultured in vitro with irradiated mononuclear cells from patients infected by HIV in the presence of PHA and polybrene. Two weeks post-HIV exposure, all 17 CD4+, but neither of the two CD8+, TCC exhibited integration of HIV in their genoma, as detected by polymerase chain reaction analysis, and released HIV into their supernatants, as detected by measuring both reverse transcriptase activity and p24 Ag. When co-cultured with either autologous or allogeneic B cells, all CD4+ HIV-infected TCC induced the synthesis of extraordinarily high amounts of IgM, IgG, and IgA. In contrast, their noninfected counterparts could provide helper function for Ig synthesis by autologous B cells only in the presence of the specific Ag (or anti-CD3 antibody), and induced allogeneic B cells to synthesize Ig only upon stimulation with anti-CD3 antibody. The supernatants of HIV-infected TCC failed to stimulate Ig synthesis in B cells. More importantly, when HIV-infected clonal T blasts and B cells were cultured in different chambers separated by a millipore membrane, permeable to molecules but not to cells, Ig synthesis did not occur. The Ig synthesis induced by HIV-infected TCC was also markedly inhibited by the addition in culture of either anti-CD4 or anti-LFA-1 antibody. In contrast, HIV-infected TCC maintained their ability to provide helper function for Ig synthesis in the absence of any stimulus, even after fixation with p-formaldehyde. These data demonstrate that in vitro infection with HIV enables human T cells to stimulate Ig synthesis by B cells by an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. This may explain, at least in part, the hypergammaglobulinemia and other phenomena related to polyclonal B cell activation frequently seen in HIV-infected persons.
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PMID:In vitro infection with HIV enables human CD4+ T cell clones to induce noncognate contact-dependent polyclonal B cell activation. 167 84

Monocyte/macrophages (MM) were isolated from HIV-1 seronegative individuals, infected with HIV-1 and examined for their ability to infect autologous T lymphocytes with and without concomitant presentation of exogenous Ag. HIV-1-infected MM presented tetanus toxin (TT) and streptokinase to T cells (as measured by [3H]thymidine incorporation) comparable to presentation by uninfected MM. In these studies, it was observed that HIV-1-infected MM without additional exogenous Ag stimulated autologous T lymphocytes, however, to a lesser degree than with TT and streptokinase. Virus production in T cells appeared to be relative to the degree of stimulation with the highest levels of stimulation and infection observed when T cells were exposed to HIV-1-infected TT-presenting MM. Studies were carried out to examine some of the restricting elements in MM-mediated infection of T lymphocytes with and without TT presentation. Antibodies to CD4, as well as soluble immunopurified gp120, blocked cell-mediated infection indicating that infection of T cells was through the CD4 molecule as has been demonstrated with cell-free virus. In addition, soluble gp120 inhibited Ag presentation by HIV-1-infected and uninfected MM. mAb to MHC class II Ag HLA-DR and -DP blocked T cell infection by HIV-1-infected MM with and without presentation of TT. No effect was observed with mAb to MHC class I Ag. These results indicate that virus transmission to T lymphocytes can be mediated by HIV-1-infected MM and that these cells maintain their function as APC. Activation of T cells appears to be important in the process of T cell infection in this system inasmuch as antibodies that block Ag presentation and thus a T cell proliferative signal inhibit infection.
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PMID:HIV-1 transmission and function of virus-infected monocytes/macrophages. 169 Feb 36

Human T cells can express MHC-class II products and were shown to be potential antigen-presenting cells. However, they are unable to capture the antigen and only antigens, which bind to T cell membranes such as the gp120 glycoprotein of HIV, are internalized, processed, and presented by T cells. To better understand the role of T cells as antigen-presenting cells, we established a method which overcomes the lack of antigen capture by T cells. Antigen (tetanus toxoid, TT) or an antigenic peptide of TT (residue 830-843, P2) was coupled to antibodies directed to T cell surface molecules such as CD2, CD4, CD8. Antibody/TT and antibody/P2 constructs stimulated P2-specific T cell clones in the absence of accessory cells, if the antibody recognized a T cell surface structure. Compared to the peptide alone, a 100-500 times lower molar concentration of the antibody/peptide construct was required to achieve a similar proliferative response. T cell stimulation via the constructs involved intracellular processing, as nonspecific, glutaraldehyde fixed T cell lines pulsed with the constructs could present the peptide and processing inhibitors like Leupeptin or Chloroquine inhibited the development of a proliferative response to the constructs. Our data underline the ability of T cells to function as antigen-processing and -presenting cells and show that antibody/antigen or antibody/peptide constructs are able to direct a certain antigen or peptide to a T cell. Antibody/peptide constructs may be interesting tools to better understand antigen processing and to study the consequences of antigen presentation by different cells.
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PMID:Use of antibody/peptide constructs of direct antigenic peptides to T cells: evidence for T cell processing and presentation. 172 68

We endeavored to study lymphoproliferative responses in children with human immunodeficiency virus (HIV) infection and to compare them with normal control children. Children were grouped according to age; 6-18 months and greater than 18 months, and according to CDC classification: asymptomatic (P1), mildly symptomatic (P2A), and advanced symptoms (P2D). Absolute CD4 and CD8 numbers were compared and found to be higher in the younger age groups. The children in P1 and P2A classes demonstrated an increase in CD8+ cells; only the children with AIDS showed a significant decrease in CD4+ cells. Lymphoproliferative responses to phytohemagglutinin A (PHA) were compared to tetanus toxoid. Only the children with acquired immunodeficiency syndrome (AIDS) (P2D) in the older group and only the symptomatic children (P2A and P2D) in the younger group showed a significant decrease in proliferative responses to PHA. All classes of infected children demonstrated a significant decrease in response to tetanus toxoid. We have been able to demonstrate a loss of antigen responsiveness which precedes the loss of mitogenic responsiveness. Furthermore, we have been able to demonstrate an age related increase in lymphoproliferative responses to both PHA and tetanus in HIV-infected and control children. Therefore, we conclude that children are particularly susceptible to the immunologic effects of HIV infection. Loss of lymphoproliferative responses to antigen occurs early in infected children and precedes the loss of CD4+ helper cells and of PHA responsiveness. This increased susceptibility to the immunopathogenesis of HIV infection is due, at least in part, to the relative immunodeficiency of infancy.
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PMID:Lymphoproliferative responses to mitogen and antigen in HIV-infected children. 174 85

IMREG-1, an immunomodulatory biological therapeutic, was studied in a placebo-controlled, double-blind, six-month trial in 45 anergic patients with AIDS-related complex (ARC) and 4 with Kaposi's sarcoma, which was followed by compassionate IMREG-1 administration to all subjects. The IMREG-1 group had significantly less AIDS-defining events compared with the placebo group during the randomized trial (6.9 events per 100 person-years vs 43.7 events per 100 person-years, P = 0.018, relative risk 6.33) and the total observation period. Patients receiving IMREG-1 significantly improved their work performance. Nine (41%) of 22 patients in the IMREG-1 group, compared with one (14%) of seven in the placebo group, recovered cutaneous reactivity to tetanus toxoid. At the end of the six-month trial, CD4+ counts were 0.429 x 10(9)/l in the IMREG-1 group and 0.304 x 10(9)/l in the placebo group (P = 0.04). IMREG-1 is a promising therapeutic for HIV-infected patients with symptoms of ARC.
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PMID:Clinical benefits and recovery of delayed-type hypersensitivity in patients with AIDS-related complex treated with IMREG-1 or placebo. 176 64

In the course of a study of lymphocyte responses to microbial antigens in HIV-infected patients, we detected a previously unrecognized phenomenon of inhibition of lymphocyte baseline proliferation, induced by the presence of tetanus toxoid and Escherichia coli in the cultures. The effects of tetanus toxoid and Escherichia coli on lymphocyte proliferation in vitro were assessed by comparing the 3H-thymidine uptake by lymphocytes cultured without stimulant with the uptake of lymphocytes cultured in the presence of the antigens. Twenty-six patients with HIV infection (20 asymptomatic/persistent generalized lymphadenopathy, 2 AIDS-related complex, 4 AIDS) were investigated and the controls were 33 healthy individuals without evidence of HIV infection. Eight out of 22 asymptomatic/PGL and ARC patients progressed to full-blown AIDS in the mean follow-up of 26 months. The inhibition of proliferation was considered to be significant when the uptake of 3H-thymidine was reduced by 20% in the presence of the antigens. Using these criteria, 50% of the patients studied with tetanus toxoid and 36% of those studied with E. coli had evidence of the inhibitory phenomenon. Seven of the eight patients who developed AIDS during the observation period had the inhibitory phenomenon. In the group of patients without the inhibitory signs only one evolved to AIDS during the follow-up. The possibility of this phenomenon being related to an induction of suppressor cell activity by the antigens is discussed.
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PMID:Inhibition of lymphocyte proliferation induced in vitro by microbial antigens in HIV-infected subjects. 180 54

We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
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PMID:Common sequence in HIV 1 GP41 and HLA class II beta chains can generate crossreactive autoantibodies with immunosuppressive potential early in the course of HIV 1 infection. 180 76

Recombinant sCD4-based proteins were evaluated for their effects on antigen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC) and for antiviral activity against PBMC infected with human immunodeficiency virus (HIVD34). Two sCD4-based proteins were solubilized, refolded, and purified to homogeneity from recombinant E. coli and consisted of the 178 amino-terminal residues of CD4 fused with the translocating and catalytic domains of Pseudomonas exotoxin A (sCD4-PE40) or 183 amino-terminal residues of CD4 (sCD4-183); a third sCD4 consisting of 369 amino acids of CD4 was purified from recombinant mammalian cells for comparative purposes (sCD4-369). Increasing molar concentrations of these sCD4s were evaluated for inhibition of PBMC proliferation induced by alloantigen (MLR), by tetanus toxoid (TTOX), or in response to crosslinking with antibody to CD3 (OKT3). In addition, the concentrations of each protein required to inhibit replication of the HIVD34 isolate in primary PBMC was determined by quantitation of HIV p24 antigen released into supernatant fluids by infected cells. By comparing antiviral activity with anti-proliferative activity a relative estimate of the selectivity index for each recombinant sCD4 was determined. Proliferation of PBMC in response to alloantigen or OKT3 was less sensitive to inhibition than proliferation induced by TTOX, and the selectivity indices estimated for sCD4-PE40 were 170, 170 and 17, respectively. The selectivity index for sCD4-183 was greater than 350 under all assay conditions. Comparative evaluation of alloantigen-stimulated proliferation with antiviral activity of sCD4-183 versus sCD4-369 suggested that the E. coli-derived sCD4-183 may have a higher selectivity index under these conditions than its mammalian cell-derived counterpart.
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PMID:Effects of a soluble CD4 and CD4-Pseudomonas exotoxin A chimeric protein on human peripheral blood lymphocytes: lymphocyte activation and anti-HIV activity in vitro. 180 85

Twenty-one asymptomatic HIV-seropositive subjects and 20 HIV-seronegative controls were assessed for their serologic response to multiple live attenuated viral, protein (toxoid), and polysaccharide vaccine antigens. Extensive in vivo and in vitro immunologic evaluations were performed. Factors predictive of immunogen responsiveness by HIV-seropositive patients were found by correlating vaccine responses with results of T- and B-cell functional assays. Eleven HIV-seropositive patients (HIV nonresponsive-NR) responded to only one of three vaccines used for analysis (meningococcus, group C; adenovirus 4, 7; and diphtheria-tetanus) compared with the normals, of whom 100% responded to two or more of the same immunogens. Ten HIV-seropositive patients (HIV responsive-R) responded equivalently to normals. The HIV NR group had distinctive immunologic abnormalities predictive of their poor immunogen responsiveness. These included defects in the T-cell helper function despite normalization of T cell number and defective T-cell suppression of Epstein-Barr virus (EBV) in vitro (HIV NR, 30% suppression; HIV R, 73% suppression; and normals, 95% suppression of EBV-driven immunoglobulin production in vitro). The B cells of the HIV NR groups were also abnormal in vivo. The HIV NR patients' B cells were larger and had increased native response to B-cell growth factor evidenced by increased thymidine incorporation. (HIV-NR, 10,232 +/- 3,003 cpm; HIV R, 5,432 +/- 1,125; normal, 402 +/- 11. HIV NR/HIV R, p less than 0.05; HIV NR/N, p less than 0.001.)(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic parameters in early-stage HIV-seropositive subjects associated with vaccine responsiveness. 182 86


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