Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morbilliviruses are highly contagious pathogens that cause some of the most devastating viral diseases of humans and animals, including measles virus (MV), canine distemper virus (CDV), and rinderpest virus (RPV). They replicate mainly in lymphoid organs throughout the body and cause severe immunosuppression accompanied with lymphopenia. We have recently shown that human, canine, and bovine signaling lymphocyte activation molecules (SLAMs; also known as CD150) act as cellular receptors for MV, CDV, and RPV, respectively. In these three morbilliviruses, all strains examined were shown to use SLAMs of their respective host species, and laboratory strains passaged on SLAM-negative cells were found to use, besides SLAM, alternative receptors, such as human CD46 for the Edmonston strain of MV. The use of SLAM as a receptor may be a property common to most, if not all, of the members of morbilliviruses. Human SLAM is a membrane glycoprotein selectively expressed on the cells of the immune system (immature thymocytes, activated lymphocytes, activated monocytes, and mature dendritic cells) and seems to mediate lymphocyte activation and to control interferon-gamma production. The destruction and/or impairment of infected SLAM-positive cells may be a mechanism for the immunosuppression induced by morbilliviruses, but other mechanisms may be also involved.
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PMID:The morbillivirus receptor SLAM (CD150). 1200 21

Immunosuppression is the major cause of infant death associated with acute measles and therefore of substantial clinical importance. Major hallmarks of this generalized modulation of immune functions are (1) lymphopenia, (2) a prolonged cytokine imbalance consistent with suppression of cellular immunity to secondary infections, and (3) silencing of peripheral blood lymphocytes, which cannot expand in response to ex vivo stimulation. Lymphopenia results from depletion, which can occur basically at any stage of lymphocyte development, and evidently, expression of the major MV receptor CD150 plays an important role in targeting these cells. Virus transfer to T cells is thought to be mediated by dendritic cells (DCs), which are considered central to the induction of T cell silencing and functional skewing. As a consequence of MV interaction, viability and functional differentiation of DCs and thereby their expression pattern of co-stimulatory molecules and soluble mediators are modulated. Moreover, MV proteins expressed by these cells actively silence T cells by interfering with signaling pathways essential for T cell activation.
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PMID:Measles virus-induced immunosuppression. 1920 13

Measles virus (MV) causes transient severe immunosuppression in patients, which may lead to secondary viral and bacterial infections, largely accounting for measles-related morbidity and mortality. MV is known to infect immune cells by using the human signaling lymphocyte activation molecule (SLAM; also called CD150) as a cellular receptor, but the mechanism by which MV causes immunosuppression is not well understood. We show that MV infection of SLAM knock-in mice, in which the V domain of mouse SLAM was replaced by the V domain of human SLAM, crossed with alpha/beta-interferon receptor knockout mice, reproduced many immunological alterations observed in human patients. These included lymphopenia, inhibition of T-cell proliferation and antibody production, increased production of the Th2 cytokine interleukin-4 (IL-4) and the immunosuppressive cytokine IL-10, and suppression of contact hypersensitivity. Gross redistribution of lymphocytes among lymphoid tissues was not apparent in infected mice, nor was an increase of regulatory T cells. The numbers of lymphocytes in lymph nodes remained almost unchanged after MV infection, despite enhanced apoptosis, suggesting that lymph nodes were replenished with lymphocytes from the peripheral blood, which may have contributed to the observed lymphopenia in the spleen. Blocking of IL-10 by use of an anti-IL-10 receptor antibody ameliorated suppression of contact hypersensitivity in infected mice. These results indicate that SLAM knock-in mice lacking the expression of the alpha/beta-interferon receptor serve as a useful small animal model with which to elucidate MV-induced immunosuppression.
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PMID:Measles virus-induced immunosuppression in SLAM knock-in mice. 2020 Feb 44

Immunosuppression is the major cause of infant death associated with acute measles. Hallmarks of this generalized modulation of immune functions include: (1) lymphopenia, (2) a prolonged cytokine imbalance consistent with suppression of cellular immunity to secondary infections and (3) silencing of peripheral blood lymphocytes that fail to expand in response to ex vivo stimulation. Lymphopenia results from depletion of T cells by mechanisms also involving MV infection, and expression of the major MV receptor CD150 plays an important role for targeting these cells. Virus transfer to T cells is thought to be mediated by dendritic cells (DCs), which are considered as central to the induction of T-cell silencing and functional skewing. MV interaction modulates functional differentiation of DCs, and thereby expression pattern of costimulatory molecules and soluble mediators. Moreover, MV proteins expressed by these cells actively silence T cells by interfering with signaling pathways essential for T-cell activation. As an essential component of this interference, the MV glycoprotein complex activates cellular sphingomyelinases in a contact-dependent manner, and these are effective at preventing stimulated rearrangements of the actin cytoskeleton and thereby morphological and functional polarization and motility of T cells.
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PMID:Measles virus-induced immunosuppression: from effectors to mechanisms. 2037 84

Transient lymphopenia is a hallmark of measles virus (MV)-induced immunosuppression. To address to what extent replenishment of the peripheral lymphocyte compartment from bone marrow (BM) progenitor/stem cells might be affected, we analyzed the interaction of wild-type MV with hematopoietic stem and progenitor cells (HS/PCs) and stroma cells in vitro. Infection of human CD34(+) HS/PCs or stroma cells with wild-type MV is highly inefficient yet noncytolytic. It occurs independently of CD150 in stroma cells but also in HS/PCs, where infection is established in CD34(+) CD150(-) and CD34(+) CD150(+) (in humans representing HS/PC oligopotent precursors) subsets. Stroma cells and HS/PCs can mutually transmit MV and may thereby create a possible niche for continuous viral exchange in the BM. Infected lymphocytes homing to this compartment may serve as sources for HS/PC or stroma cell infection, as reflected by highly efficient transmission of MV from both populations in cocultures with MV-infected B or T cells. Though MV exposure does not detectably affect the viability, expansion, and colony-forming activity of either CD150(+) or CD150(-) HS/PCs in vitro, it efficiently interferes with short- but not long-term hematopoietic reconstitution in NOD/SCID mice. Altogether, these findings support the hypothesis that MV accession of the BM compartment by infected lymphocytes may contribute to peripheral blood mononuclear cell lymphopenia at the level of BM suppression.
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PMID:Wild-type measles virus interferes with short-term engraftment of human CD34+ hematopoietic progenitor cells. 2159 50

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression.IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells in vivo However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to in vitro MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.
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PMID:In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells. 2943 64