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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections caused by lentiviruses, including human immunodeficiency virus, are characterized by slowly progressive disease in the presence of a virus-specific immune response. The earliest events in the virus-host interaction are likely to be important in determining disease establishment and progression, and the kinetics of these early events following lentiviral infection are described here. Lymphatic cannulation in the sheep has been used to monitor both the virus and the immune response in efferent lymph after infection of the node with maedi-visna virus (MVV). Viral replication and dissemination could be detected and consisted of a wave of MVV-infected cells leaving the node around 9 to 18 days postinfection. No cell-free virus was recovered despite the fact that soluble MVV p25 was detected in lymph plasma. The maximum frequency of MVV-infected cells was only 11 in 10(6) but over the first 20 days of infection amounted to greater than 10(4) virus-infected cells leaving the node. There was a profound increase in the output of activated lymphoblast from the lymph nodes of infected sheep, characterized by an increased percentage of CD8+ lymphoblasts. All of the CD8+ lymphoblasts at the peak of the response expressed both major histocompatibility complex class II DR and DQ molecules but not interleukin-2 receptor (CD25). The in vitro proliferative response of efferent lymph cells existing the node after challenge with MVV to both recombinant human interleukin-2 and the mitogen concanavalin A was decreased between days 8 and 16 postinfection, and a specific proliferative response to MVV was not detected until after day 15. Despite the high level of CD8+ lymphoblasts in efferent lymph, direct MVV-specific cytotoxic activity was demonstrated in only one of the five MVV-challenged sheep. MVV-specific antibody responses, including neutralization and MVV p25 immune complexes in efferent lymph, were detectable during the major period of virus dissemination. The relationship of these findings to the evasion of the host's acute immune response by MVV is discussed.
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PMID:Early events in immune evasion by the lentivirus maedi-visna occurring within infected lymphoid tissue. 839 44

Two different populations of infected T cells are present in human immunodeficiency virus (HIV)-infected individuals: activated cells that produce virions and quiescent cells that harbor the viral genome but are unable to produce virus unless they are activated. Using an in vitro model of acute HIV infection, we have evaluated the effect of depleting activated T cells with an immunotoxin and subsequently inhibiting activation of quiescent T cells with an immunosuppressive agent. CD25 (Tac, p55), the alpha chain of the interleukin 2 receptor, is expressed on activated, but not quiescent, T cells. An anti-CD25-ricin A chain immunotoxin eliminated activated, CD25+ HIV-infected cells and, thereby, inhibited viral production by these cells. Subsequent addition of cyclosporine to the residual CD25- cells prevented their activation and thereby suppressed their ability to produce virus and to propagate the infection to uninfected T cells.
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PMID:Combined use of an immunotoxin and cyclosporine to prevent both activated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus. 843 1

The in situ content of cells of the reticuloendothelial system and lymphatic cells was examined in the skin of eight symptom-free HIV-positive individuals, three AIDS patients and eleven healthy immunocompetent volunteers. The epidermis was obtained in vivo by the suction blister technique. The numbers of CD68+, CD3+, CD8+, CD25-(IL2R)+ and HLA-DR+ intraepidermal cells proved to be independent of the number of CD4+ peripheral blood lymphocytes. At the same time, the intraepidermal concentrations of these cells were generally low in symptom-free HIV-infected individuals. The strong inverse correlation between the number of epidermal Langerhans cells (LC) and the severity of immunodeficiency was quantitatively confirmed; an increase in LC in symptom-free HIV-infected individuals was found. Thus, the reduction in these cells which was observed in the epidermis of AIDS patients began at a significantly elevated level. In contrast to results from other studies, in AIDS patients, in the present study, the concentration of epidermal LC did not differ significantly from that of healthy immunocompetent volunteers. The immunohistochemical technique can be as effective as in situ hybridization for the detection of HIV in the skin. Our results suggest that the viral load of the skin is rather low in HIV-infected subjects. HIV was demonstrated in one cell of one AIDS case by in situ techniques and this result was confirmed by a polymerase chain reaction examination using the same amount of tissue as for the in situ techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution and infection of Langerhans cells in the skin of HIV-infected healthy subjects and AIDS patients. 844 79

There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be putative targets for immunotherapeutic approaches. Peripheral blood T lymphocytes are capable of suppressing monoclonal immunoglobulin production of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or interleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocytes as demonstrated in a cytotoxicity assay using purified MM plasma cells as targets. The lytic activity is significantly higher when the effectors are prestimulated with irradiated autologous MM plasma cells. Based on these results 18 MM patients of advanced stages with tumor progress received 9 x 10(6) IU/m2 recombinant IL-2 (Proleukin) twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for five subsequent days per week s.c. from days 3-56 (q 12 weeks). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by CD25 antigen expression and CD56+ natural killer (NK) cells expanded in the peripheral blood. NK cell activity and lymphokine-activated killer cell activity were significantly enhanced. IL-2 therapy induced endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations. Tumor response was observed in 6/17 evaluable patients. These data indicate that low-dose IL-2 treatment can stimulate immune enhancement in MM patients despite their characteristic tumor-induced immunodeficiency, and has proven to have limited efficacy in advanced MM patients.
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PMID:Tumor-directed cytotoxicity in multiple myeloma--the basis for an experimental treatment approach with interleukin 2. 852 May 15

It has been shown that the combined use of two pharmacologic agents can inhibit human immunodeficiency virus (HIV) production by peripheral blood mononuclear cells in vitro. One, an anti-CD25 immunotoxin (IT), kills activated T cells that produce virus; the other, the immunosuppressive drug cyclosporine, prevents the quiescent cells, which harbor HIV, from becoming activated. The present study compares the antiviral activities of two agents, SDZ NIM811 and FK506, to that of cyclosporine. In combination with the anti-CD25 IT, these drugs significantly suppressed virus production. In the absence of prior addition of the IT, the ability of the drugs to inhibit virus production was much lower, suggesting that they work effectively in latently infected cells. In the case of SDZ NIM811, the inhibition of virus production was accompanied by a modest inhibition of cell proliferation. In contrast, FK506 exerted strong antiproliferative activity. Cyclosporine was both moderately antiproliferative and a potent antiviral agent.
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PMID:The use of cyclosporine, FK506, and SDZ NIM811 to prevent CD25- quiescent peripheral blood mononuclear cells from producing human immunodeficiency virus. 884 28

The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, induces an acutely lethal disease in experimentally inoculated pigtailed macaques, that is characterized by severe enteropathy and extensive immune activation, particularly within gut-associated lymphoid tissue (GALT). Experiments were conducted to determine whether virally induced immune activation might promote the induction of apoptosis in GALT during acute SIVsmmPBj14 infection. In situ labeling studies revealed a significant increase in the number of apoptotic cells within GALT from macaques with acute SIVsmmPBj14 infection, compared to (i) other tissues from the same animals, (ii) GALT from virus-negative animals, or (iii) GALT from macaques that were sacrificed soon after infection with SIVmac239, which does not cause acutely lethal enteropathy. These findings were confirmed by biochemical assays of DNA fragmentation, using DNA laddering and ELISA techniques. Immunostaining experiments revealed a strong positive correlation between the extent of apoptosis and the degree of immune activation, as assessed either by the number of cells which contained nuclear (activated) RelA or by the number of cells immunoreactive for CD25, a T-cell activation marker. Additional analyses of SIV antigen expression revealed that the majority of the apoptotic cells were not productively infected by SIV (i.e., that they were bystander cells). Taken together, these findings support the hypothesis that SIVsmmPBj14 efficiently induces immune activation and that this results in extensive apoptosis within gut-associated lymphoid tissue during acute viral infection.
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PMID:Apoptosis correlates with immune activation in intestinal lymphoid tissue from macaques acutely infected by a highly enteropathic simian immunodeficiency virus, SIVsmmPBj14. 891 30

Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune function reflected in reduced lymphocyte proliferative responses. Many other immune changes are induced by HIV-1, but their relationship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease parameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decreased cell surface expression of the interleukin-2 receptor (CD25), (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of serum immune complex dissociated p24 antigen. However, impaired function was not associated with increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlated with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altered function are cell surface molecules with significant roles in lymphocyte proliferation and were associated primarily with CD4 cells, compatible with the view that dysregulation of CD4 cells is responsible for impaired function.
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PMID:Relation of impaired lymphocyte proliferative function to other major human immunodeficiency virus type 1-induced immunological changes. 900 83

Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the interleukin-2 receptor alpha chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin 2. This immunodeficiency is characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B cell development. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1, and furthermore they fail to normally down-regulate levels of the anti-apoptotic protein bcl-2.
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PMID:Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor. 909 64

IL-2 was initially defined as a T lymphocyte growth factor, but recent studies have provided evidence that it may also play a role in regulating T cell differentiation, apoptosis, and tolerance. To examine the contribution of IL-2 to these processes, we have bred a class II-restricted TCR transgene into mice deficient in the alpha-chain of the IL-2R, CD25. We show that in response to Ag, T cells from these mice are unable to use IL-2 and, as a result, are less efficient at traversing the cell cycle, and proliferate less than wild-type cells. Furthermore, CD25 -/- T cells exhibit reduced survival in vitro, even in the presence of costimulatory signals. IL-4 and IL-15, a cytokine related to IL-2, enhance the survival and Ag-induced proliferation of CD25 -/- T cells. Activated CD25 -/- T cells are resistant to Fas-mediated activation-induced cell death (AICD), and this defect cannot be corrected by other cytokines. Therefore, IL-2 plays a unique role in regulating AICD, but has redundant roles in T cell survival and proliferation in vitro. The failure of AICD observed with CD25 -/- T cells may explain the unexpected observation that deficiency of IL-2 or of the alpha- or beta-chain of the IL-2R results not in immunodeficiency, but in autoimmune disease.
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PMID:Functional responses and apoptosis of CD25 (IL-2R alpha)-deficient T cells expressing a transgenic antigen receptor. 910 38

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated by virus-encoded regulatory proteins, as well as by a variety of cellular factors. Productive infection of human T lymphocytes by HIV-1 is dependent upon the activation status of the target cells. In general, short-term mitogenic stimulation of CD4 T cells is used to enhance infection of peripheral blood mononuclear cells (PBMC) in vitro. Recently, we demonstrated that adoptive transfer of human PBMC into lethally irradiated BALB/c mice, radioprotected with severe combined immunodeficiency (SCID) mouse bone marrow, leads to marked T-cell activation and proliferation. In the present study, we investigated the effect of such xenoactivation of human T cells on their susceptibility to HIV-1 infection. Human cells that were recovered from human/Balb radiation chimeras supported efficient replication of laboratory strains of HIV-1, as well as of HIV-1 clinical isolates. The multiplicity of infection required to attain effective virus replication in the recovered xenoactivated human cells was 10- to 100-fold lower than that needed for infection of short- or long-term phytohemagglutinin (PHA)-stimulated blasts or of various T-cell lines. Analysis of human cell surface activation markers has indicated that xenoactivation in the mouse, in contrast to in vitro stimulation with PHA, is associated with a marked downregulation of CD25 (interleukin 2 receptor). Our results demonstrate that human cells recovered from human/Balb radiation chimeras, which are hypersensitive to HIV-1 infection, differ from in vitro-stimulated cells in their activation status. Therefore, this system could be used to study host factors that participate in HIV-1 infection and replication in vitro and in vivo.
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PMID:Human T cells recovered from human/Balb radiation chimeras are hypersensitive to human immunodeficiency virus type 1 infection. 915 41


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