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

While cell-mediated immunity is known to play an important role in controlling viral infections, its role in human and experimental animal models of human AIDS has not been established. To address this issue, four juvenile rhesus macaques were infected with simian immunodeficiency virus SIVMAC. Freshly isolated peripheral blood mononuclear cells from these SIVMAC-infected macaques and four uninfected control macaques were assessed for T-cell proliferative activity to SIV, monthly, for 10 consecutive months. T cells from SIV-infected monkeys failed to proliferate in response to SIV added directly to the culture. However, when SIV was processed by autologous antigen-presenting cells prior to culture with purified T cells, proliferative responses were uniformly demonstrated in SIV-infected monkeys, but not in uninfected controls. Proliferation in response to heat-inactivated SIV was mediated by CD4+ T cells and was shown to be MHC class II-restricted. However, the proliferative response to infectious SIV was mediated by both CD4+ and CD8+ T cells and was MHC class-restricted. As disease progressed, a decline in the T-cell proliferative response was observed.
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PMID:Simian immunodeficiency virus-specific T-cell-mediated proliferative response of infected rhesus macaques. 216 69

The development of acute graft-vs-host disease (GVHD) is a common outcome after the injection of fully MHC disparate parental T cells into unirradiated F1 mice. Murine cytomegalovirus (MCMV) infection has been previously shown to augment the development of acute GVHD in the parent-into-F1 (P----F1) model, such that 10-fold fewer parental cells are required. In the present study, we have investigated the effect of MCMV infection on the induction of non-lethal GVHD that occurs in P----F1 combinations involving MHC class I only or class II only differences. Using P----F1 combinations involving either an H-2K only difference or an H-2D only difference, MCMV infection of F1 mice 3 days before the injection of parental spleen cells led to a profound T cell immunodeficiency that strongly resembled that observed in acute GVHD. Further studies examining the H-2K disparate P----F1 combination, C57Bl/6---- (C57Bl/6xB6.C-H-2bm1) F1 and combined MCMV infection showed that the immunodeficiency is characterized by a profound loss of in vitro Th cell production of IL-2 and an intrinsic defect in T effector function as shown by an inability of rIL-2 to restore defective CTL responses. Additional experiments in these mice revealed the presence of suppressor cells as well as significant parent-anti-F1 CTL activity possibly accounting for the suppressor effect. This pattern of immunodeficiency was not seen after the administration of either MCMV or MHC class I disparate parental cells alone. MCMV infection did not detectably alter the immunodeficiency observed in a P----F1 combination involving a MHC class II difference only. These results indicate that MCMV infection can alter the pattern of GVHD in the setting of an MHC class I disparity, but not in the setting of class II disparity, such that it resembles acute GVHD. These results may have relevance to the human transplant setting where intercurrent CMV infection has been associated with an adverse clinical outcome.
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PMID:Synergistic effect of murine cytomegalovirus on the induction of acute graft-vs-host disease involving MHC class I differences only. Analysis of in vitro T cell function. 217 81

Immunoelectron microscopy was applied to study the antigenic make-up of human and simian immunodeficiency viruses (HIV, SIV) grown in cells expressing either MHC class I (Molt-3) or MHC class I and II (H9) antigens. A variety of antibodies directed against the surface glycoprotein gp120 of HIV and against MHC class I and II antigens were employed. Consistent with earlier observations on the loss of HIV envelope components, gp120 was only weakly demonstrable on the mature virion. MHC class I determinants were present regularly in small amounts on HIV and SIV. Class II antigens, e.g. HLA-DR were found in high density on HIV and SIV grown in H9 cells, but were absent, as expected, on virus grown in Molt-3 cells. These cellular surface antigens are constituents of the virion. The presence of MHC class II antigens in virus preparations used for diagnostic purposes might explain some of the false positive results in HIV serology. Possible biological implications of these virus associated cellular antigens for the pathogenicity of HIV are discussed.
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PMID:MHC-antigens: constituents of the envelopes of human and simian immunodeficiency viruses. 245 27

The MHC class II CID represents an example of immunodeficiency in which the defect in expression of membrane glycoproteins leads to abnormal cell to cell interactions and thus to abnormal immune responses. It represents an interesting model which confirms the importance of MHC molecules in all immune responses to foreign antigens. It also underlines the complexity of regulatory mechanism which control the expression of MHC class II genes. To elucidate these mechanisms, it is essential to identify and characterize the genes involved in control of MHC class II expression.
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PMID:Combined immunodeficiency with abnormal expression of MHC class II genes. 246 26

In this report we have attempted to review our knowledge of the role(s) of CD4 in human T-cell function and the consequences of interactions between CD4 molecules and the human immunodeficiency virus (HIV). The observation in 1981 that antibodies to certain epitopes of CD4 inhibited the immune functions of CD4+ T cells led to the initial suggestion that CD4 molecules play a direct role in T-cell function. Although the precise functions of CD4 remain incompletely understood, a preponderance of evidence suggests that this molecule may in fact serve several critical roles. At least one such role is that of interacting directly with MHC class II molecules on antigen-presenting cells, presumably facilitating cell-to-cell interactions. On activated CD4+ T cells, CD4 molecules can also interact directly with the T-cell receptor complex to influence the immune response. Unfortunately, in addition to interacting with the T-cell receptor and class II MHC determinants, CD4 serves as a high affinity receptor for HIV, the causative agent of AIDS. Not only does interaction between the virus and CD4 initiate viral fusion to the cell membrane and HIV entry but, in addition, a similar molecular interaction initiates fusion between HIV-infected and uninfected CD4+ cells, resulting in the formation of multinucleated syncytia. Since uninfected CD4+ cells are, in effect, recruited into such syncytia, this mechanism may account in part for the depletion of CD4+ T cells in HIV-infected patients. Soluble forms of CD4 produced either by genetic engineering or solid phase peptide synthesis can completely block HIV infectivity and syncytia formation in vitro, remarkably without apparent effects on T-cell immunity. Such molecules are currently being explored for their possible therapeutic effects on HIV infection in vivo.
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PMID:Role of CD4 in normal immunity and HIV infection. 247 27

MHC class II deficiency is an inherited immunodeficiency disease characterized by the presence of a normal number of T and B lymphocytes and profound anomaly of cellular and humoral responses to foreign antigens. All bone-marrow-derived cells (including B lymphocytes, monocytes and activated T lymphocytes) and also enterocytes and endothelial cells do not express all HLA class II (DR, DQ and DP) molecules on their membrane. It is known that the proper recognition of foreign antigens depends on their presentation, together with HLA class II molecules, on the membrane of antigen-presenting cells. MHC class II deficient combined immunodeficiency confirms the important role of MHC gene products in immune-defence mechanisms. Patients suffer from repeated and severe infections that are frequently the cause of death. The defect in HLA class II expression is the consequence of a lack of synthesis of HLA class II alpha and beta chains in patients' cells. Studies performed at DNA and RNA levels showed that there was no gross abnormality of MHC class II genes and that mRNA for all HLA molecules was not detected in patients' cells. These results, together with segregation studies performed in several families, suggested that the defect in HLA class II gene expression involves a transacting regulatory factor. Direct transcription assays showed that the disease is characterized by an absence of HLA class II gene transcription. An analysis of the specific binding of nuclear proteins from patients' cell lines to HLA class II promotor showed that a specific protein, RF-X, which normally binds to a regulatory sequence common to HLA class II promotors, is affected in MHC class II combined immunodeficiency.
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PMID:Combined immunodeficiency with defective expression in MHC class II genes. 251 9

Interactions of CD4 with the class II major histocompatibility complex (MHC) are crucial during thymic ontogeny and subsequently for helper and cytotoxic functions of CD4+CD8- T lymphocytes. CD4 is the receptor for the T-lymphotropic human immunodeficiency virus and binds its envelope glycoprotein, gp120. The residues involved in gp120 binding have been localized to a region within the immunoglobulin-like domain I of CD4, which corresponds to CDR2 of an immunoglobulin variable region, but the CD4 residues important in MHC class II interaction have not been characterized. Here, using a cell-binding assay dependent specifically on the CD4-MHC class II association, we analyse the effects of mutations in CD4 on class II versus gp120 binding. Mutations in CDR2 that destroy gp120 binding affect CD4-MHC class II binding similarly. In addition, binding of soluble gp120 to CD4-transfected cells abrogates their ability to interact with class II-bearing B lymphocytes. In contrast, other mutations within domains I or II that have no effect on gp120 binding eliminate or substantially decrease class II interaction. Thus, the CD4 binding site for class II MHC is more complex than the gp120 binding site, possibly reflecting a broader area of contact with the former ligand and a requirement for appropriate juxtaposition of the two N-terminal domains. The ability of gp120 to inhibit the binding of class II MHC to CD4 could be important in disrupting normal T-cell physiology, acting both to inhibit immune responses and to prevent differentiation of CD4+CD8+ thymocytes into CD4+CD8- T lymphocytes.
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PMID:Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. 254 30

Chicken anaemia agent (CAA) causes severe anaemia, loss of body weight, and hypoplasia of thymus at day 14 after inoculation of one-day-old chickens. Several reports have described an enhancement of concurrent infections with f.e. Marek's disease virus, Infectious Bursal Disease virus, and Reovirus. Immunohistochemical methods were used to describe the immunopathological lesions of the thymus that probably form the basis of the immunodeficiency caused by CAA. Monoclonal antibodies and antisera against leucocytes, T lymphocytes, CD4, B lymphocytes, mononuclear phagocytes, MHC class II, and keratin were used. At day 14 after inoculation, the thymic cortex was completely depleted of thymocytes, whereas the medulla was not. T-cell areas in the spleen also lacked T lymphocytes. In contrast the cortex still contained stromal cells with MHC class II molecules and keratin. At day 21, the cortex had completely regenerated and all clinical signs of CAA infection had disappeared. Labelling experiments with BrdU in 4-week-old control chickens demonstrated that 25% of the divided cells was detected in the medulla and 75% in the cortex. The tissue tropism of CAA may, apart from the preference for rapidly dividing cells, be directed by specific cell determinants.
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PMID:Transient depletion of cortical thymocytes induced by chicken anaemia agent. 256 Feb 70

The human immunodeficiency virus (HIV) and the closely related simian immunodeficiency virus (SIV) induce profound immune dysfunction in primate species. The present studies show that cell populations infected in vitro with SIV exhibit increases in major histocompatibility complex (MHC) class II antigen expression. Cell lines chronically infected with both the monkey and human viruses express substantially more MHC class II but not more lineage-restricted or activation antigens on their membranes than do uninfected cell lines. Furthermore, 2'-deoxy-5-iodouridine increased MHC class II antigen expression on SIV-infected cell lines in parallel with increased expression of viral antigens. MHC class II induction does not appear to be mediated through the production of a soluble factor, such as gamma interferon, by SIV-infected cells. Interestingly, studies of the kinetics of antigen expression by cell lines after SIV infection indicate that the induction of MHC class II structures is a late event. Immunoelectron microscopy revealed that MHC class II antigen is expressed not only on the surfaces of the SIV-infected cells but also on the envelope of virus particles derived from those cells. MHC antigen expression on virus-infected cells and the expression of those determinants by the virus may play a role in the pathogenesis of acquired immunodeficiency syndrome and the autoimmune abnormalities observed in HIV-infected individuals.
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PMID:Simian immunodeficiency virus induces expression of class II major histocompatibility complex structures on infected target cells in vitro. 303 70

The CD4 (T4) antigen was originally described as a phenotypic marker specific for helper T cells, and has recently been shown to be the receptor for the human immunodeficiency virus (HIV). Functional studies using monoclonal antibodies directed at CD4 and major histocompatibility complex (MHC) class II molecules led to the suggestion that CD4 binds to the MHC class II molecules expressed on stimulator cells, enhancing T-cell responsiveness by increasing the avidity of T cell-stimulator cell interaction and/or by transmitting a positive intracellular signal. But recent evidence that antibodies to CD4 inhibit T-cell responsiveness in the absence of any putative ligand for CD4 has been interpreted as suggesting that antibody-mediated inhibition may involve the transmission of a negative signal via the CD4 molecule instead. We have infected a murine T-cell hybridoma that produces interleukin 2 (IL-2) in response to human class II HLA-DR antigens with a retroviral vector containing CD4 cDNA. The resulting CD4-expressing hybridoma cell lines produce 6- to 20-fold more IL-2 in response to HLA-DR antigens than control cell lines. Furthermore, when antigen levels are suboptimal, the response of the cell lines is entirely CD4-dependent. The data presented here clearly demonstrate that CD4 can enhance T-cell responsiveness and may be crucial in the response to suboptimal levels of antigen.
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PMID:Expression and function of CD4 in a murine T-cell hybridoma. 303 88


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