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)

Trypsinization of human T-lymphocytes removes surface receptors which bind to sheep erythrocytes (E). Human dialyzable leukocytes extracts (DLE) and thymosin (Fraction V) have been shown to significantly increase the rate of regeneration of T-lymphocyte E-receptors. Both physical-chemical and immunochemical results reported herein indicate that the enhancing effect of human DLE preparations on the rate of regeneration of T-lymphocyte E-receptors is due at least in part to the presence of thymosin alpha 1-peptide in these preparations. Thymosin alpha 1-peptide purified from thymosin Fraction V and putative thymosin alpha 1 preparations purified from human DLEs were each active not only in increasing the rate of regeneration of T-lymphocyte E-receptors removed by trypsinization but also were active in vitro in markedly increasing the number of E-rosetting cells in two patients with immunodeficiency disease manifested in part as a reduction in the normal percentage of mature T-lymphocytes capable of forming E-rosettes.
Thymus 1984
PMID:Dialyzable leukocyte extracts contain thymosin. 646 97

The X-linked lymphoproliferative syndrome (XLP) is characterized by a combined variable immunodeficiency with vulnerability to Epstein-Barr virus (EBV)-induced fatal or chronic infectious mononucleosis, acquired agammaglobulinemia, aplastic anemia, or malignant B cell lymphomas. Diagnosis of XLP requires documentation of two or more maternally related males with these phenotypes. Epstein-Barr virus must be demonstrated in circulating blood, lymphoid tissues, or saliva of infected males. Characteristically, the patients have low-titer antibodies to EBV and often lack anti-EB nuclear-associated antibody due to T cell defects. Thymus gland is often depleted and epithelium may be destroyed. Thymic-dependent regions in lymph nodes and spleen are depleted and immunoblastic transformation with plasma cell differentiation is seen. The carrier females exhibit partial immune deficiency and have paradoxically elevated antibodies to EBV. Our registry of XLP provides consultation and comprehensive study of persons and families with the syndrome.
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PMID:X-linked lymphoproliferative syndrome. An immunodeficiency disorder with acquired agammaglobulinemia, fatal infectious mononucleosis, or malignant lymphoma. 689 75

Due to self-renewal of the peripheral pool of T-cells, adult thymectomy has normally little influence on immunocompetence. However, thymus might play a more important role in the setting of viral-induced cytopathic effects on T-cells in the periphery. Therefore, thymus weight, cell numbers, and subset distribution were sequentially analysed after infection with RadLV-Rs, a viral mixture known to induce murine retrovirus induced immunodeficiency (MAIDS). Infection induced thymic atrophy (concerning organ weight as well as total cell number) which culminated seven weeks after inoculation. The atrophic process mostly reflected the depletion of double positive CD4+ CD8+ cells since their proportion sharply decreased around week 6. Single positive T-cells were less affected by the process. The proportion of B-cells progressively increased. Surprisingly, there was a strong correlation between the extent of atrophy and the frequency of B-cells in the thymus. Finally, an abnormal CD4+ T-cell subset lacking Thy-1 and previously described in the periphery also appeared in the thymus and its frequency was strongly correlated with the expansion of B-cells in this organ.
Thymus 1994
PMID:Thymus involvement in murine acquired immunodeficiency (MAIDS). 753 29

SCID mice were engrafted with human foetal liver, thymus and lung. Human cells were subsequently detected among peripheral blood leukocytes for 81% of tested animals and in tissue implants for 100% of tested animals. SCID-hu mice received intraperitoneal injections of human immunodeficiency virus type 1 (HIV1) at from 20 up to 20,000 median tissue culture infectious doses (TCID5). HIV1 infection was detected by means of cell culture and polymerase chain reaction both in blood and implants, up to 58 days after infection. The rate of infection was dependent upon the inoculated dose: the frequency of thymus infection ranged from 14% with 20-500 TCID50 up to 100% with 20,000 TCID50. HIV1 infection was detected less frequently in blood leukocytes than in thymus. Thymus virus load ranged from 40 to 50,000 HIV1 provirus copies per million cells and was not correlated with either infectious dose or viraemia. Thymus T-cell depletion was observed mainly in the CD1+4+8+ immature thymocyte compartment. The same rate of SCID-hu mouse infection was obtained using three different primary HIV1 isolates, suggesting that infection was not restricted to a few particular virus strains. The systemic infection of SCID-hu mice following intraperitoneal virus injection mimics some traits of human HIV infection and provides a promising, novel approach for future investigations in this field.
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PMID:Dose-dependent systemic human immunodeficiency virus infection of SCID-hu mice after intraperitoneal virus injection. 763 34

The anti-retrovirus cell-mediated immunity was repeatedly investigated in seven monkeys (Macaca sylvana). Four of these animals were injected with cell-free supernatants containing human immunodeficiency viruses: two monkeys received HIV1 Bru (2.5 x 10(6) cpm), two received HIV2 Rod (1.5 x 10(6) cpm). Two additional animals were injected with a cell-free supernatant containing simian immunodeficiency virus SIV/mac 251 (1.5 x 10(6) cpm) and the last animal served as control. The four macaques infected with HIV2 Rod and SIV/mac 251 seroconverted. Freshly isolated and non stimulated peripheral blood mononuclear cells from these infected macaques and from the uninfected control were repeatedly assessed for cytolytic activity. Target cells consisted of heterologous human cell lines expressing HIV1 Bru, HIV2 Rod or SIV/mac proteins. A significant cytotoxic activity, non-restricted at the major histocompatibility complex class I (MHC-I), was demonstrated in one HIV2 Rod-infected animal (F8) and in one SIV/mac 251-infected animal (M1). This last animal showed progressively diminishing cytolytic activity that was correlated with a pronounced decrease in CD4+ lymphocytes. An AIDS-like disease developed in M1, with presence of lymphadenopathy, weight loss, diarrhea and opportunistic infections. Cytotoxic activity was active against SIV and HIV2-infected target cells in an MHC-unrestricted manner; it was specific to virus-infected cells and there was cross-reactivity between HIV2 and SIV. Cytotoxic effectors appeared to be mainly CD8+ cells. This model may prove to be very useful in evaluating the capacity of candidate AIDS vaccines to elicit effective cell-mediated immune responses.
Thymus 1993 Aug
PMID:MHC-I non-restricted cytotoxic activity in Macaca sylvana experimentally inoculated with HIV2 and SIV/mac. 790 83

Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including increased sensitivity of lymphocytes to ionizing radiation, neurologic dysfunction, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes. Past work has documented an inability to establish cultured T cell lines, and abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in the wst/wst mouse relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from the wasted and control mouse for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (which has been associated with apoptosis) in thymic lymphocytes and to a lesser extent in spinal cord in the wst/wst mouse relative to controls; expression of Rp-2 and Tcl-30 mRNA (also reported to be induced during apoptosis) were not detectable in spleen or thymus. Expression of Rp-2, Rp-8, and Tcl-30 mRNA in other affected tissues of the wasted mouse (brain and liver) were similar in the wasted mouse and controls. Thymus and spleen from the wasted mouse have reduced numbers of viable cells relative to controls. Higher spontaneous DNA fragmentation was observed in lymphocytes from the wasted mouse than in controls; however, gamma-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in lymphocytes derived from the wasted mouse relative to controls. These results suggest that high spontaneous and gamma-ray-induced apoptosis in T cells of the wasted mouse may contribute to the mechanism underlying the observed lymphocyte and DNA repair abnormalities.
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PMID:Expression of enhanced spontaneous and gamma-ray-induced apoptosis by lymphocytes of the wasted mouse. 860 55

The thymus attempts to ensure that T cells which emerge from it are able to discriminate self from nonself. As such, it is a potential 'backdoor' through which microbial parasites can enter, manipulate the host into perceiving them as 'self', and thereby avoid immune surveillance. It is proposed that the host has evolved to overcome this parasitic strategy by rapidly producing large numbers of long-lived T cells very early in life (closing the backdoor), before the developing individual has significant contact with infectious organisms, and while still under the protection of its mother's intact immune system. Hence the capacity of the thymus to function efficiently early in the lifespan would have been strongly favored by natural selection. It is well established in evolutionary biology that strong selection favoring enhanced early function easily accommodates, through pleiotropy, the accumulation of later occurring negative effects, and it is through this process that thymic involution and subsequent immune system senescence may have evolved. Once a large pool of competent T cells has been produced, even those microbes capable of contaminating the thymus usually can be eliminated, or at least contained. However, microbes that both destroy peripheral T cells (particularly peripheral T cells that are activated against them), and contaminate the thymus (leading to deletion of potential replacements of the destroyed peripheral cells), may be able to eventually overcome the immune system, thus producing disease after a long period of apparent latency. Human immunodeficiency virus, which is initially well controlled by the immune system, may become unleashed via this process.
Thymus
PMID:Microbial parasites versus developing T cells: an evolutionary 'arms race' with implications for the timing of thymic involution and HIV pathogenesis. 862 77

Thymus alterations associated with feline immunodeficiency virus (FIV), an AIDS animal model, were investigated by measuring phenotypic composition of thymocytes, structure of thymic epithelial cells, and transcription of viral RNA in the thymus of FIV-infected juvenile kittens. These kittens either acquired infection by natural vertical transmission or were experimentally inoculated with the virus at defined times of fetal or neonatal life. Thymocytes from FIV-infected cats were analyzed by flow cytometry for the differential expression of CD4, CD8, Pan T, and IgG and subpopulation percentages were compared to values from uninfected littermates. Infected cats demonstrated a decrease in the percentage of CD4+/CD8+ lymphocytes and a concurrent increase in the percentage of CD4-/CD8-, CD4-/CD8+, and IgG+ lymphocytes. Absolute numbers of IgG+ cells were increased with FIV infection. On bivariate distribution scatter plots generated by two-color flow cytometry, this population of IgG+ cells overlapped extensively with cells having low to minimally detectable levels of a pan-T lymphocyte marker, suggesting that thymocytes were coated with IgG. Immunohistochemical detection of feline IgG defined a broad zone of IgG+ cells within the residual cortex but outside lymphoid follicles. However, cells stained with B5, a feline B lymphocyte marker, localized almost exclusively to the centers of lymphoid follicles that were also characterized by a lack of internal cytokeratin staining. FIV RNA transcripts detected by in situ hybridization using an FIVgag RNA probe were evenly distributed throughout the thymic parenchyma except in lymphoid follicles, which were generally devoid of FIV expression. Despite these phenotypic and structural changes, thymus weight, expressed as a percentage of body weight, was not significantly reduced. From these data, we conclude that the clinically asymptomatic stage of FIV infection is associated with two distinct B cell-related phenomena within the thymus-the formation of germinal centers and the coating of thymocytes with IgG. These changes accompany a distorted thymocyte distribution characterized by a reduced percentage of CD4+/CD8+ lymphocytes and a relative increase in CD4-/CD8+ and CD4-/CD8- lymphocytes. Together, these findings suggest that degenerative thymic changes after lentivirus infection may involve humoral immune mechanisms.
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PMID:Selective thymocyte depletion and immunoglobulin coating in the thymus of cats infected with feline immunodeficiency virus. 913 79

A decrease in natural killer (NK) cell activity is a common feature of the immune dysfunction found in patients with human immunodeficiency virus (HIV)-induced acquired immune deficiency syndrome (AIDS). The present study was aimed at exploring the NK and the lymphokine-activated killer (LAK) cell activities of lymphocytes from HIV-seropositive subjects. The in vitro production of interleukins (IL-2 and IL-10) in response to mitogens was also studied. Two groups of HIV-seropositive subjects were studied: asymptomatic and AIDS patients. Controls were normal blood donors. The NK cell activity in peripheral blood mononuclear cells (PBMC) from AIDS patients was significantly lower than that in PBMC from both HIV-seronegative subjects and asymptomatic patients. There was no significant difference between asymptomatic patients and controls. Exposure of PBMC from all three groups of individuals to an optimal dose of IL-2 in vitro enhanced LAK cell activity. At all three effector: target cell ratios, the LAK activity in AIDS patients remained below that in normal subjects. However, the proportional increase of lytic activity with IL-2 was slightly higher in AIDS patients than in HIV-seronegative subjects. The mitogen-induced production of IL-2 was especially reduced in AIDS patients. In contrast, very high levels of mitogen-induced production of IL-10 were found in the AIDS group, as compared to asymptomatic subjects or to controls. We therefore conclude that the alteration of NK cell activity occurs at an advanced stage of HIV infection, that the reduction of cytotoxic activity is partially restored by exogenous IL-2, and that decreased production of IL-2 and increased production of IL-10 may account for part of this reduction in cytotoxicity.
Thymus 1997
PMID:Interleukin (IL)-2 deficiency aggravates the defect of natural killer cell activity in AIDS patients. 915 80

T-cell mediated cytotoxicity play an important role in the control of human immunodeficiency virus (HIV) infection. The polyclonal cytotoxic T lymphocyte (CTL) response against target cells infected with a recombinant vaccinia virus expressing Env, Gag, Nef or reverse transcriptase (RT) proteins has been studied in four groups of individuals: acquired immune deficiency syndrome (AIDS) patients, AIDS-related complex (ARC) patients, HIV-1 seropositive subjects and seronegative controls. CTL lines have been generated by non-specific stimulation with phytohemagglutinin and interleukin-2 and target cells have been prepared from autologous B lymphocytes. CTL from asymptomatic and ARC individuals recognized most of the various proteins of HIV-1 but those from AIDS patients had very low or absent responses to the majority of proteins, with the anti-Nef cytotoxic activity decreasing first. Two of 10 AIDS patients had demonstrable recognition of Gag p24, one of RT and eight patients had no recognition of any of the proteins. The effector cells were demonstrated to be predominantly of the CD8+ phenotype, using the appropriate monoclonal antibodies. When heterologous target cells were substituted for autologous cells, the cytotoxic response was abrogated in the vast majority of cases demonstrating its human leucocyte antigen (HLA) class I restriction. Among the 10 HIV-seronegative subjects, nine had no CTL activity against the various HIV-1 proteins but one subject was able to recognize Env and RT. In the evolution of HIV infection from the seropositive stage to AIDS, CTL polyclonal activities progressively decrease, with Nef responses disappearing first, then Env and Gag p55, followed by RT and Gag p24.
Thymus 1997
PMID:Loss of T-cell cytotoxic responses in the course of HIV-1 infection. 949 84


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