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At least 55 records · Page 3Linked to original sources
PubMed2006

Hypogammaglobulinemia and exacerbated CD8 T-cell-mediated immunopathology in SAP-deficient mice with chronic LCMV infection mimics human XLP disease.

The human genetic disease X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A/SAP that encode SLAM-associated protein (SAP), is characterized by an inability to control Epstein-Barr virus (EBV) and hypogammaglobulinemia. It is unclear which aspects of XLP disease are specific to herpesvirus infection and which reflect general immunologic functions performed by SAP. We examined SAP- mice during a chronic LCMV infection, specifically to address the following question: Which SAP deficiency immunologic problems are general, and which are EBV specific? Illness, weight loss, and prolonged viral replication were much more severe in SAP- mice. Aggressive immunopathology was observed. This inability to control chronic LCMV was associated with both CD8 T-cell and B-cell response defects. Importantly, we demonstrate that SAP- CD8 T cells are the primary cause of the immunopathology and clinical illness, because depletion of CD8 T cells blocked disease. This is the first direct demonstration of SAP- CD8 T-cell-mediated immunopathology, confirming 30 years of XLP clinical observations and indirect experimentation. In addition, germinal center formation was extremely defective in chronically infected SAP- animals, and hypogammaglobulinemia was observed. These findings in a chronic viral infection mouse model recapitulate key features of human XLP and clarify SAP's critical role regulating both cellular and humoral immunity.

Agammaglobulinemia↗
PubMed1992

Effect of microbial immunomodulants on the course of LCMV infection in old mice with thymus involution.

Old mice with thymus involution were treated intraperitoneally with a live vaccine containing a mesogenic strain of attenuated Newcastle Disease Virus or with Mannozym (M, 1% zymosan suspension). One day after the treatments mice were infected with lymphocytic choriomeningitis virus (LCMV) intracerebrally. The fatal course of the consequent LCMV infection was stimulated by each of the pretreatments, indicating that the cellular immune response was stimulated. The results are compared with results of experiments carried out on suckling, young adult and old mice in similar experimental systems. The authors' previous publication suggesting that the direction and degree of the immunomodulant effect may be influenced by the actual age-dependent condition of the lymphoid system, have been confirmed.

Adjuvants, Immunologic↗
PubMed1986

Effect of attenuated viral vaccines on suckling mice infected with LCMV.

A single intraperitoneal treatment with live Newcastle Disease Virus (NDV) containing attenuated NDV vaccine, and with live infectious bursal disease virus (IBDV) containing attenuated IBDV vaccine, one day before intracerebral infection with lymphocytic choriomeningitis virus (LCMV) increased, whereas a similar treatment with inactivated NDV or IBDV vaccine did not influence the death rate of suckling mice from experimental lymphocytic choriomeningitis. Thus the attenuated live vaccine stimulated, whereas the inactivated ones failed to affect the cell-mediated immune response to LCMV. Control studies set up with the supernatant of plain tissue culture routinely used for the propagation of IBDV have shown that unlike the attenuated NDV vaccine, the immunostimulatory action is associated not so much with the virus itself, as with an as yet unidentified component of the tissue culture supernatant.

Animals↗
PubMed1998

Modulation of the cellular immune response to intracerebral lymphocytic choriomeningitis virus (LCMV) infection in mice.

Certain viruses do not kill the cells they infect. The immunological response of the host in such situations may be involved in the development of pathologic changes and clinical illness. Pioneering work by Rowe has shown that death associated with acute LCMV infection in the mouse is resulted from the immune response. Many investigators using a variety of techniques including neonatal thymectomy, irradiation, or treatment of adult mice with antilymphoid drugs or antithymocyte sera have confirmed and extended Rowe's observations. The study of LCMV and the disease it causes in its natural murine host has provided the initial findings that open new fields in viral immunobiology, viral immunopathology, and cell-cell recognition.

Acute-Phase Reaction↗
PubMed1999

Lymphocytic responses and the gradual hippocampal neuron loss following infection with lymphocytic choriomeningitis virus (LCMV).

Infection of rats with LCMV is known to cause a bi-phasic neurodegeneration characterized by acute T lymphocyte-mediated cerebellar damage, followed by gradual hippocampal neuron loss that occurs by an undefined mechanism. We found infiltration of CD8 + T-cells (but not CD4 + or NK cells) in the hippocampus which correlated with the acute phase, but not the chronic hippocampal degenerative phase. While immunosuppression of T lymphocytes protected the cerebellum and revealed the infection of corticohippocampal glia, the degeneration in the hippocampus was unabated. These data suggest that T lymphocytes control glial infection and mediate degeneration in the cerebellum but not the hippocampus.

Animals↗
PubMed2002

A structural basis for LCMV immune evasion: subversion of H-2D(b) and H-2K(b) presentation of gp33 revealed by comparative crystal structure.Analyses.

LCMV infection of H-2(b) mice generates a CD8(+) CTL response mainly directed toward three immunodominant epitopes. One of these, gp33, is presented by both H-2D(b) and H-2K(b) MHC class I molecules. The virus can escape immune recognition in the context of both these MHC class I molecules through single mutations of the peptide. In order to understand the underlying structural mechanism, we determined the crystal structures of both complexes. The structures reveal that the peptide is presented in two diametrically opposed manners by H-2D(b) and H-2K(b), with residues used as anchor positions in one MHC class I molecule interacting with the TCR in the other. Importantly, the peptide's N-terminal residue p1K protrudes from the binding cleft in H-2K(b). We present structural evidence that explains the functional consequences of single mutations found in escape variants.

Animals↗
PubMed1998

Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice.

Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN-gamma is redundant in the afferent phase of the antiviral T cell response as well as a local mediator of this T cell mediated inflammatory disease. However, IFN-gamma may play an indirect role as it is involved in reducing extraneural infection that may compete with CNS for available effector cells. Analysis of the inflammatory exudate disclosed that leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production of tumor necrosis-alpha and NO) was significantly impaired. Notably, a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may be induced in the absence of IFN-gamma and local macrophage activation.

Animals↗
PubMed1999

Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses.

Using a variety of techniques, including limiting dilution assays (LDA), intracellular IFNgamma assays, and Db-IgG1 MHC dimer staining to measure viral peptide-specific T cell number and function, we show here that heterologous virus infections quantitatively delete and qualitatively alter the memory pool of T cells specific to a previously encountered virus. We also show that a prior history of a virus infection can alter the hierarchy of the immunodominant peptide response to a second virus and that virus infections selectively reactivate memory T cells with distinct specificities to earlier viruses. These results are consistent with a model for the immune system that accommodates memory T cell populations for multiple pathogens over the course of a lifetime.

Animals↗