scholarly journals Mechanisms of suppression of cytotoxic T-cell responses in murine lymphocytic choriomeningitis virus infection.

1977 ◽  
Vol 145 (5) ◽  
pp. 1131-1143 ◽  
Author(s):  
M B Dunlop ◽  
R V Blanden
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Lymphoid Tissues ◽  
High Dose ◽  
High Level

The cytotoxic T-cell response to lymphocytic choriomeningitis (LCM) virus infection was suppressed either in vitro or in vivo by addition of a high level of syngeneic virus-infected cells or syngeneic cells from congenital LCM virus carriers to the environment of the responding cells. This effect was not duplicated by formaldehyde-fixed carrier cells, nor could it be accounted for by 'cold' target competition by carrier cells at the level of the cytotoxicity assay. Conversely, suppression was produced in vivo by water-lysed, ultrasonically treated carrier cell suspensions, or by a large dose of LCM virus equivalent to that contained in the carrier cells. Thus a high level of infectious virus was a common factor in all observed examples of suppression. Based upon this, the following hypothesis, a form of 'forbidden clone deletion,' was proposed to account for virus-specific cytotoxic T-cell tolerance in LCM virus congenital carriers, or in high dose suppression. A high level of virus in lymphoid tissues, while not cytopathic per se, may result in infection of all or most T cells; this then may lead to deletion either via 'suicide' of individual, infected, cytotoxic T cells with receptors specific for virus-induced antigenic patterns on their own surface membranes, or by mutual lysis of two adjacent T cells.

scholarly journals Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

1990 ◽  
Vol 171 (5) ◽  
pp. 1815-1820 ◽  
Author(s):  
P Aichele ◽  
H Hengartner ◽  
R M Zinkernagel ◽  
M Schulz
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Lymphocytic Choriomeningitis ◽  
Effector T Cells ◽  
T Cell Response ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Effector T Cell

Induction in vivo of antiviral cytotoxic T cell response was achieved in a MHC class I-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in IFA. The effector T cells are CD8+, restricted to the class I Ld allele of the analyzed mouse strain, and are specific both at the level of secondary restimulation in vitro and at the effector T cell level. These results suggest that cocktails of viral peptides may be used as antiviral T cell vaccines.

scholarly journals Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells.

1978 ◽  
Vol 147 (4) ◽  
pp. 1236-1252 ◽  
Author(s):  
T J Braciale ◽  
K L Yap
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Response ◽  
Infectious Virus ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell

This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.

scholarly journals Expression of a MHC class II transgene determines both superantigenicity and susceptibility to mammary tumor virus infection.

1993 ◽  
Vol 178 (4) ◽  
pp. 1441-1445 ◽  
Author(s):  
C Pucillo ◽  
R Cepeda ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Infection ◽  
Mhc Class Ii ◽  
Mammary Tumor ◽  
Class Ii ◽  
T Cell Response ◽  
Mammary Tumor Virus ◽  
Tumor Virus

Milk-borne mouse mammary tumor virus (MMTV) is a type B retrovirus that induces mammary carcinoma. Infectious MMTV, as well as genomically integrated mouse mammary proviruses, encode superantigens that are recognized by T cells that express appropriate T cell receptor V beta products. To determine the relationship between the superantigenic property of milk-borne MMTV and its in vivo infectivity, mice which were either positive or negative for expression of a transgene-encoded E alpha E beta class II major histocompatibility complex (MHC) product were exposed to milk borne C3H MMTV. Superantigen-mediated deletion of V beta 14-expressing T cells occurred only in E alpha transgene-positive mice, indicating that the deletion was E alpha E beta dependent. When mice were analyzed for viral infection by assaying viral p28 in the milk of recipient females, significant p28 levels were found only in E alpha E beta transgene-positive mice. Similarly, the presence of C3H MMTV LTR mRNA in mammary glands, as detected by PCR, paralleled p28 levels. These findings indicate that E alpha expression or the E alpha-dependent T cell response to viral superantigen is causally related to susceptibility to MMTV infection, and that lack of a permissive class II product can protect mice from virus infection.

scholarly journals High-Dose Borna Disease Virus Infection Induces a Nucleoprotein-Specific Cytotoxic T-Lymphocyte Response and Prevention of Immunopathology

2001 ◽  
Vol 75 (23) ◽  
pp. 11700-11708 ◽  
Author(s):  
Esther Furrer ◽  
Thomas Bilzer ◽  
Lothar Stitz ◽  
Oliver Planz
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Disease Virus ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
High Dose ◽  
Immune Reactivity ◽  
Borna Disease Virus ◽  
Cell Functions ◽  
Borna Disease

ABSTRACT Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8+ T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426–434, 1995) have reported protection against Borna disease after inoculation of high-dose cell-adapted BDV. Here we show that the outcome of the infection, i.e., immunopathology versus protection, is simply dependent on the amount of virus used for infection. High-dose BDV (106 FFU) triggers an early virus-specific reaction of the immune system, as demonstrated by strong cellular and humoral responses. In particular, the early presence and function of nucleoprotein-specific CD8+ T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persistent virus infection, high-dose input virus mediates early control of the pathogen due to an efficient induction of an antiviral immune mechanism. From these data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infection is established.

scholarly journals T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay?

1986 ◽  
Vol 164 (4) ◽  
pp. 1075-1092 ◽  
Author(s):  
R M Zinkernagel ◽  
E Haenseler ◽  
T Leist ◽  
A Cerny ◽  
H Hengartner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Cytotoxic T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Cytotoxic T Cell ◽  
Release Assay ◽  
Kinetics Of ◽  
Dose Dependent

A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens. The donor cell dose-dependent increase of these enzymes was first measurable 6-18 h after transfer with 2 X 10(8) cells or 3 X 10(6) cells, respectively. The time-dependent increase caused by the adoptive transfer of 1-2 X 10(8) cells was strictly linear during a period of up to 25-40 h. These results indicate single-hit kinetics of liver cell death and suggest that effector T cells destroy infected liver cells via direct contact rather than via soluble toxic mediators. The results may represent the best in vivo correlate of the in vitro 51Cr-release assay that has been analyzed so far, and strongly support the view that antiviral cytotoxic T cells are directly cytolytic in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity

2010 ◽  
Vol 207 (9) ◽  
pp. 1891-1905 ◽  
Author(s):  
Magali Irla ◽  
Natalia Küpfer ◽  
Tobias Suter ◽  
Rami Lissilaa ◽  
Mahdia Benkhoucha ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Response ◽  
Lymphoid Tissues ◽  
Capture Process

Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4+ T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag–specific contacts with CD4+ T cells. These interactions promote the selective expansion of myelin-Ag–specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4+ T cells in vivo.

scholarly journals Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model

Gut ◽  
2017 ◽  
Vol 67 (8) ◽  
pp. 1525-1535 ◽  
Author(s):  
Sepideh Levander ◽  
Fredrik Holmström ◽  
Lars Frelin ◽  
Gustaf Ahlén ◽  
Daniel Rupp ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Hepatoma Cells ◽  
T Cell Response ◽  
Hcv Infection ◽  
Cytotoxic T Cell ◽  
Hcv Rna

ObjectiveHCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.

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