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)

Dendritic cells (DC) are specialized antigen-presenting leukocytes that are responsible for the activation of naive as well as memory T lymphocytes. If infected by human immunodeficiency virus (HIV), DC may transfer virus to CD4+ lymphocytes. However, the question of whether DC are infected in vivo is controversial. As HIV infection is more active in secondary lymphoid organs than in blood, infection of splenic DC isolated from HIV-seropositive patients was investigated. Splenic DC were first enriched and characterized by flow cytometry from HIV- donors. After direct isolation, they were negative for monocyte and T- and B-lymphocyte markers, negative for CD1a, but positive for major histocompatibility complex class II and CD4. After in vitro maturation, major histocompatibility complex class II expression increased, while CD4 expression was lost. Extensive purification from the spleens of seven HIV+ patients was performed by fluorescence-activated cell sorting. The frequency of cells harboring HIV DNA in purified populations was quantified by limiting-dilution PCR. Directly isolated DC (average, 1/3,000; range, 1/720 to 1/18,000) were in each patient 10 to 100 times less infected than CD4+ T lymphocytes (average, 1/52; range, 1/17 to 1/190). On average, 1/1,450 (1/320 to 1/6,100) unseparated mononuclear splenocytes (containing 5% CD4+ lymphocytes) harbored HIV DNA. In conclusion, in these HIV+ patient spleens, DC seem to be infected, but HIV-DNA positive CD4+ T lymphocytes accounted for the vast majority of infected mononuclear splenocytes.
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PMID:Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients. 760 39

The B cell antigen B7 delivers a strong co-stimulatory signal for the activation of T cells by binding to its ligands CD28 and CTLA4. Here we demonstrate the surface expression of the B7 molecule on activated human T cells in vitro and under certain conditions in vivo and its functional importance in T-T cell interactions. B7 was detected by flow cytometry on antigen-specific CD4+ and allospecific CD8+ cloned T cells from different donors with anti-B7 monoclonal antibody (mAb) or a soluble CTLA4-C gamma 1 chimera molecule and by reverse transcription-polymerase chain reactions. The expression of B7 was up-regulated following restimulation of the T cell clones and peaked after 7-9 days. Moreover, we show that the B7 molecule on T cells is functionally involved in T-T cell interactions: mAb to CD28 and the CTLA4-Ig fusion protein could inhibit the proliferation of specific T cell clones in response to T cells as antigen-presenting cells (APC) or the proliferation of peripheral blood mononuclear cells in a primary allostimulation with activated T cells as stimulator cells. Finally, we found that B7 can be expressed on freshly isolated circulating T cells since in a preliminary study with a limited number of patients, B7 was present on a subset of CD3+ cells. B7 was expressed on activated T cells (CD4+ and CD8+) of certain human immunodeficiency virus (HIV)-infected individuals (0.5-20% B7+CD8+ cells) or some patients with autoimmune diseases whereas CD3+ cells of healthy individuals did not express B7. The coexpression of major histocompatibility complex class II molecules and B7 may be relevant for the capacity of activated T cells to function as APC. The expression of B7 on T cells in vivo in autoimmune diseases and in HIV infection may be important for a better understanding of these diseases.
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PMID:The B7 adhesion molecule is expressed on activated human T cells: functional involvement in T-T cell interactions. 769 Mar 23

Cryptosporidium parvum preparations were studied for their ability to induce specific proliferation of cultured human peripheral blood mononuclear cells (PBMC) from both immunocompetent and human immunodeficiency virus-positive persons, some of whom had transient cryptosporidiosis. The proliferation of PBMC from sensitized donors induced by C. parvum preparations was due mainly to antigen-specific rather than nonspecific activation, as indicated by the kinetics of the proliferative response, inhibition of the PBMC proliferation by a monoclonal antibody directed against major histocompatibility complex class II-specific HLA-DR molecule, and lack of proliferation of umbilical cord blood PBMC. PBMC from immunocompromised patients did not proliferate in response to C. parvum-specific antigens. The supernatants of PBMC obtained from immunocompetent donors contained interleukin-10 and interferon (IFN)-gamma after PBMC were exposed to C. parvum preparations. High IFN-gamma values were found in patients who had recovered from cryptosporidiosis, suggesting that IFN-gamma plays a role in resolving this infection.
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PMID:Crude extract and recombinant protein of Cryptosporidium parvum oocysts induce proliferation of human peripheral blood mononuclear cells in vitro. 779 13

Cellular adherence is important for monocyte migration and function and is known to induce monocyte activation, leading to the production of mRNA for several proto-oncogenes and cytokines. In addition, since cellular adherence has important intracellular signalling function, it has the potential to enhance human immunodeficiency virus (HIV) replication in monocytic cells. We have investigated the effects of adhesion of the monocytic cell line THP-1 transfected with HIV1 or HIV2 long terminal repeat chloramphenicol acetyltransferase (LTR CAT) constructs. These studies have shown that adherence to tissue culture plastic or confluent endothelial cells is essential for enhanced HIV LTR CAT expression in lipopolysaccharide-stimulated cells. In addition, we have investigated the effects of engagement of specific adhesion molecules, using immobilized antibodies, on HIV replication in the promonocytic cell line OM101, which contains a single latent proviral copy of HIV. Such studies have demonstrated that engagement of CD18, the beta subunit of the lymphocyte function-related antigen-1 (LFA-1) and major histocompatibility complex class II (MHC II) enhanced HIV replication. LFA-1 is involved in both monocyte-endothelial cell interactions and monocyte-T-cell interactions, and MHC II is involved in monocyte interaction with antigen-specific T cells. These data suggest that such interactions of membrane adhesion molecules with their appropriate ligand enhance HIV replication in vivo. Thus, this study has demonstrated that cellular adherence is a key regulatory factor of HIV replication in monocytic cells.
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PMID:Cellular adherence enhances HIV replication in monocytic cells. 780 Sep 38

CD4, a T cell receptor for major histocompatibility complex class II antigen, is a key regulator of immunological reactivities. When engaged together with the T cell antigen receptor, CD4 enhances immune reactions, whereas when ligated independently of the antigen receptor CD4 inhibits the activation of T cells or initiates their deletion. CD4 serves also as a receptor for the human immunodeficiency virus (HIV), which binds the receptor with high avidity through its envelope molecule, gp120. Studies in tissue culture have shown that its affinity to CD4 gives the virus opportunities to utilize CD4-mediated signaling and to manipulate immunocytes. We show here in human CD4 transgenic mice that appropriately cross-linked HIV envelope protein causes massive deletion of HIV-reactive T cells in vivo.
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PMID:Deletion of T lymphocytes in human CD4 transgenic mice induced by HIV-gp120 and gp120-specific antibodies from AIDS patients. 791 36

Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and immunodeficiency induced by a replication-defective murine leukemia virus (BM5def) that encodes Pr60gag as its only product. It has been suggested that the gag polyprotein is responsible for vigorous antigenic stimulation of CD4+ T cells and generalized secondary activation of the immune system. This model was tested first by infecting mice (C2K/O) that lack class II major histocompatibility complex molecules required for presentation of antigens to CD4+ T cells. C2K/O mice expressed BM5def at high levels but did not develop MAIDS either when unmanipulated or following transfer of CD4+ T cells. Second, B6 mice reconstituted with C2K/O bone marrow cells had normal frequencies of B cells (class II negative) and CD4+ cells and expressed high levels of BM5def transcripts but did not develop MAIDS; however, MAIDS developed in class II-competent nu/nu mice reconstituted with CD4+ T cells and in C2K/O mice reconstituted with B6 bone marrow to give class II-positive B cells and with purified CD4+ T cells. These results indicate that induction of MAIDS by BM5def is antigen driven and is dependent on expression of major histocompatibility complex class II molecules on antigen-presenting cells and the presence of CD4+ T cells.
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PMID:Murine AIDS is an antigen-driven disease: requirements for major histocompatibility complex class II expression and CD4+ T cells. 791 49

Activated human T cells express major histocompatibility complex class II proteins, and their potential to present antigens to T cell clones has been documented extensively. The effect of such TT presentation on responder T cell clones has been shown to be the induction of tolerance, sometimes accompanied by activation. To investigate whether freshly isolated responder T cells are also susceptible to such induction of tolerance by activated T cells functioning as antigen-presenting cells (APC), we have used the capability of unprimed ex vivo T cells to respond in a proliferation assay in vitro to alloligands on professional APC. We show that purified human T cells ex vivo, when exposed to alloligand on activated T cells for primary allorecognition in vitro, fail to mount a proliferative response. Priming of responder CD4+ T cells with alloligand expressed on activated T cells results in the induction of nonresponsiveness to a subsequent challenge by competent allo-APC. This ability of activated, HLA-DR+ T cells to induce nonresponsiveness to subsequent challenge in bulk CD4+ T cell populations ex vivo has interesting implications for infections involving T cells such as human immunodeficiency virus.
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PMID:Induction of tolerance in freshly isolated alloreactive CD4+ T cells by activated T cell stimulators. 792 75

Either of two structurally related major histocompatibility complex class II alleles, DRB1*1102, which encodes a DR5 specificity, or DRB1*1301, which encodes a DR6 specificity, was found in 67% of individuals responding to human immunodeficiency virus type 1 (HIV-1) infection with a syndrome characterized by persistent circulating and diffusely infiltrative CD8 lymphocytosis (DILS), slow progression to opportunistic infections, and delayed CD4 T-cell depletion. These alleles were present in only 28% of ethnically matched HIV-positive controls (P = 0.001). The frequency of DRB1*1301 was increased in both Blacks and Caucasians with this syndrome, while that of DRBI*1102 was increased only in Blacks, where 80% had either of these alleles. To investigate whether the host response associated with these alleles influences the evolutionary divergence of the HIV-1 genome, sequencing of the envelope V3 loop was performed. This revealed a significantly diminished lymphocyte viral heterogeneity compared with random HIV+ controls matched for CD4 T-cell levels. These results suggest that the immunogenetics of the host influence the nature of the immune response to HIV-1, which may lead to constrained evolution of HIV-1 gene products. Of possible relevance, the alpha-helical third diversity region common to both the DRB1*1102 and DRB1*1301 allelic products was noted to have homology with the C-terminal region of the HIV-1 envelope V3 loop at six of nine consecutive residues. This suggests the possibility that these alleles may bias the anti-HIV T-cell receptor repertoire through a mimicry mechanism.
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PMID:Certain HLA-DR5 and -DR6 major histocompatibility complex class II alleles are associated with a CD8 lymphocytic host response to human immunodeficiency virus type 1 characterized by low lymphocyte viral strain heterogeneity and slow disease progression. 797 86

Infection of the rhesus monkey with simian immunodeficiency virus of macaques (SIVmax) was employed to explore the early immune events associated with the initial containment of an acute AIDS virus infection. In nine rhesus monkeys infected intravenously with uncloned SIVmac strain 251, high-level p27 plasma antigenemia was usually detected transiently from approximately day 7 through day 21 following virus inoculation. SIVmac replication in lymph nodes measured by in situ RNA hybridization closely paralleled the time course and magnitude of viremia. The containment of SIVmac spread by 3 to 4 weeks following infection suggests an efficient, early immune control of this virus infection. Anti-SIVmac antibodies were first detected in the blood at approximately day 14. At the time antigenemia was decreased or cleared, SIVmac neutralizing antibodies were present. A rise in circulating and lymph node CD8+ T cells also occurred coincident with the clearance of antigenemia and persisted thereafter. These CD8+ lymphocytes in lymph nodes had increased expression of both major histocompatibility complex class II and the adhesion molecule LFA-1; they also demonstrated decreased expression of the naive T-cell-associated CD45RA molecule. SIVmac-specific cytotoxic T-lymphocyte precursors were detected in both blood and lymph node by 7 days post-virus inoculation. These studies indicate that both virus-specific humoral and cellular immune mechanisms in blood and lymph node are associated with the clearance of viremia that occurs within the first month of infection of rhesus monkeys with SIVmac.
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PMID:Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. 813 22

In asymptomatic human immunodeficiency virus-1 infection T cells respond normally to allogeneic dendritic cells (DC), but DC show reduced stimulatory capacity. By contrast in HTLV-1 infection no significant changes in allogeneic stimulation were seen but DC-stimulated activity of autologous T cells. In seeking animal models relevant to these diseases the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendritic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stimulate allogeneic T cells from healthy animals. MLV at the same concentration did not significantly affect the ability of DC to stimulate allogeneic T cells, but provoked considerable enhancement of the low level stimulation by DC in the syngeneic system. Similar results were obtained following in vivo exposure to viruses. Two pieces of evidence suggested that these effects were due to impairment of DC function and were not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with untreated allogeneic DC caused no significant alteration in T cell activity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultured in the presence of zidovudine. Treatment of DC by RLV caused a decrease of cluster formation with allogeneic T cells. No statistically significant influence of MLV was observed on cluster formation after 3-h of incubation in the allogeneic system. However, after 18-h incubation MLV-treated DC formed fewer clusters with T cells than untreated DC. At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA-1 receptor expression on the DC surface in mice infected by RLV. MLV induced no significant changes. These mouse retroviruses can therefore cause changes in DC function similar to those already reported using human retroviruses and may provide models for studying their effects.
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PMID:Effects of murine leukemia viruses on the function of dendritic cells. 822 70


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