scholarly journals Infection of lymphocytes by a virus that aborts cytotoxic T lymphocyte activity and establishes persistent infection.

1991 ◽  
Vol 174 (1) ◽  
pp. 203-212 ◽  
Author(s):  
P Borrow ◽  
A Tishon ◽  
M B Oldstone
Keyword(s):  
Immune System ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Persistent Infection ◽  
Infectious Virus ◽  
Cytotoxic T Lymphocyte ◽  
Lymphoid Tissues ◽  
Wild Type ◽  
Ctl Response ◽  
Adult Mice

For viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. When inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (LCMV ARM) induces a CD8(+)-mediated cytotoxic T lymphocyte (CTL) response that clears the infection within 7-14 d (CTL+ [P-]). By contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a CTL response and are thus able to establish a persistent infection in adult mice (CTL- [P+]). This report compares the interaction of CTL+ (P-) and CTL- (P+) viruses with cells of the immune system. Both types of virus initially bind to 2-4% of CD4+ and CD8+ T lymphocytes and replicate within cells of both subsets. The replication of CTL- (P+) and CTL+ (P-) viruses in lymphocytes in vivo is similar for the first 5 d after initiating infection. Thereafter, in mice infected with CTL- (P+) variants, lymphocytes retain viral genetic information, and infectious virus can be recovered throughout the animals' lives. In contrast, when adult mice are infected with wild-type CTL+ (P-) LCMV ARM, virus is not recovered from lymphocytes for greater than 7 d after infection. A CD8(+)-mediated anti-LCMV CTL response is induced in such mice. Clearance of infected lymphocytes is produced by these LCMV-specific CTLs, as shown by their ability to lyse lymphocytes expressing LCMV determinants in vitro and the fact that depletion of CD8+ lymphocytes before infection with CTL+ (P-) viruses results in levels of infected lymphocytes similar to those found in undepleted CTL- (P+)-infected mice. Hence, CTL-mediated lysis of T lymphocytes carrying infectious virus is a critical factor determining whether virus persists or the infection is terminated.

scholarly journals H-2Db−/− Mice Are Susceptible to Persistent Infection by Theiler's Virus

2000 ◽  
Vol 74 (12) ◽  
pp. 5470-5476 ◽  
Author(s):  
Arièle Azoulay-Cayla ◽  
Sven Dethlefs ◽  
Béatrice Pérarnau ◽  
Eva-Lotta Larsson-Sciard ◽  
François A. Lemonnier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Lymphocyte ◽  
Persistent Infection ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
Theiler's Virus ◽  
Ctl Response ◽  
The Central Nervous System

ABSTRACT H-2b mice are resistant to persistent infection of the central nervous system by Theiler's virus. They clear the infection 7 to 10 days after intracranial inoculation. Resistance maps to the H-2D gene and not to the H-2K gene and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) response. We used H-2b mice in which theH-2D or the H-2K gene had been inactivated to dissect the respective roles of these genes in resistance. We report that H-2D −/− but notH-2K −/− mice were susceptible to persistent infection. Furthermore, whereas H-2K −/−mice mounted a vigorous virus-specific CTL response, similar to that of control C57BL/6 mice, the CTL response ofH-2D −/− mice was nil or minimal. Using target cells transfected with the H-2Db or theH-2Kb gene, we showed that theH-2K-restricted CTL response against the virus was minimal in H-2D −/− mice. These results demonstrate that the H-2Db andH-2Kb genes play nonredundant roles in the resistance to this persistent infection.

scholarly journals Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses

2001 ◽  
Vol 75 (21) ◽  
pp. 10139-10148 ◽  
Author(s):  
Wei Shi ◽  
Jianzhong Liu ◽  
Yujun Huang ◽  
Liang Qiao
Keyword(s):  
Dna Vaccine ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Oral Immunization ◽  
Lymphocytic Choriomeningitis ◽  
Lymphoid Tissues ◽  
Adjuvant Effect ◽  
Ctl Response ◽  
Lymphocyte Responses ◽  
Ctl Responses

ABSTRACT Intestinal mucosa is a portal for many infectious pathogens. Systemic immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and skin, we determined whether PV pseudovirus, i.e., PV-like particles in which unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid) encoding the same epitope given systemically. The virus-like particles that were used to make the pseudoviruses provided an adjuvant effect for induction of CTLs by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic lymphoid tissues when administered orally. Oral immunization with the pseudovirus encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses. In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL response in intestinal mucosal lymphoid tissue. Further, oral immunization with the human PV pseudovirus encoding E7 protected mice against mucosal challenge with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as a novel vaccine to induce mucosal and systemic CTL responses.

scholarly journals Thymic selection and adaptability of cytotoxic T lymphocyte responses in transgenic mice expressing a viral protein in the thymus.

1994 ◽  
Vol 180 (5) ◽  
pp. 1901-1910 ◽  
Author(s):  
M G von Herrath ◽  
J Dockter ◽  
M Nerenberg ◽  
J E Gairin ◽  
M B Oldstone
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocytic Choriomeningitis ◽  
Target Cells ◽  
Viral Glycoprotein ◽  
Specific Lysis ◽  
Ctl Response ◽  
Selection Processes ◽  
Np Gene

Upon primary challenge with lymphocytic choriomeningitis virus (LCMV), H-2d (BALB/cByJ) mice mount a cytotoxic T lymphocyte (CTL) response to a single immunodominant domain of the viral nucleoprotein (NP) but no detectable response to the viral glycoprotein (GP). To manipulate this CTL response, the viral NP gene was expressed in the thymus and peripheral T lymphocytes using the murine Thy1.2 promoter. As a result, such Thy1.2-NP (H-2d) transgenic (tg) mice deleted their high-affinity anti-LCMV-NP CTL, but generated equal numbers of lower-affinity NP CTL. Further, they made an alternative anti-LCMV-GP CTL response that is not normally found in non-tg mice indicating a hierarchial control of the CTL response. Unlike the H-2d mice, H-2b (C57Bl/6J) mice normally mount a CTL response to both LCMV-GP and -NP. When the LCMV-NP was expressed using the Thy1.2 promoter in these H-2b mice, the LCMV-NP-specific CTL response was completely aborted and no CTL to new, alternative viral epitopes were generated. Dilutions of H-2b or H-2d NP peptides indicated that 3-4 logs less H-2b NP peptide was required to sensitize syngeneic target cells for CTL-specific lysis, suggesting that the differing affinities of H-2b and H-2d major histocompatibility complex molecules for their peptides likely account for the total removal of NP CTL in the H-2b mice but only partial removal in H-2d mice made to express thymic NP. Thymic grafting experiments done with thymi from newborn Thy1.2-NP tg mice show that selection processes studied in this model are of central (thymic) origin and are not caused by Thy1.2-positive LCMV-NP-expressing T lymphocytes in the periphery.

scholarly journals Expression of Interleukin-4 by Recombinant Respiratory Syncytial Virus Is Associated with Accelerated Inflammation and a Nonfunctional Cytotoxic T-Lymphocyte Response following Primary Infection but Not following Challenge with Wild-Type Virus

2005 ◽  
Vol 79 (15) ◽  
pp. 9515-9526 ◽  
Author(s):  
Alexander Bukreyev ◽  
Igor M. Belyakov ◽  
Gregory A. Prince ◽  
Kevin C. Yim ◽  
Katie K. Harris ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Response ◽  
T Lymphocyte ◽  
Primary Infection ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Wild Type ◽  
Ctl Response ◽  
Syncytial Virus

ABSTRACT The outcome of a viral infection or of immunization with a vaccine can be influenced by the local cytokine environment. In studies of experimental vaccines against respiratory syncytial virus (RSV), an increased stimulation of Th2 (T helper 2) lymphocytes was associated with increased immunopathology upon subsequent RSV infection. For this study, we investigated the effect of increased local expression of the Th2 cytokine interleukin-4 (IL-4) from the genome of a recombinant RSV following primary infection and after a challenge with wild-type (wt) RSV. Mice infected with RSV/IL-4 exhibited an accelerated pulmonary inflammatory response compared to those infected with wt RSV, although the wt RSV group caught up by day 8. In the first few days postinfection, RSV/IL-4 was associated with a small but significant acceleration in the expansion of pulmonary T lymphocytes specific for an RSV CD8+ cytotoxic T-lymphocyte (CTL) epitope presented as a major histocompatibility complex class I tetramer. However, by day 7 the response of tetramer-positive T lymphocytes in the wt RSV group caught up and exceeded that of the RSV/IL-4 group. At all times, the CTL response of the RSV/IL-4 group was deficient in the production of gamma interferon and was nonfunctional for in vitro cell killing. The accelerated inflammatory response coincided with an accelerated accumulation and activation of pulmonary dendritic cells early in infection, but thereafter the dendritic cells were deficient in the expression of B7-1, which governs the acquisition of cytolytic activity by CTL. Following a challenge with wt RSV, there was an increase in Th2 cytokines in the animals that had previously been infected with RSV/IL-4 compared to those previously infected with wt RSV, but the CD8+ CTL response and the amount of pulmonary inflammation were not significantly different. Thus, a strong Th2 environment during primary pulmonary immunization with live RSV resulted in early inflammation and a largely nonfunctional primary CTL response but had a minimal effect on the secondary response.

scholarly journals Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

2000 ◽  
Vol 191 (9) ◽  
pp. 1499-1512 ◽  
Author(s):  
Franziska Lechner ◽  
David K.H. Wong ◽  
P. Rod Dunbar ◽  
Roger Chapman ◽  
Raymond T. Chung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Acute Infection ◽  
Hcv Infection ◽  
Ctl Response ◽  
Acute Hcv ◽  
Ifn Γ ◽  
Acute Hcv Infection

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

scholarly journals Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment.

1995 ◽  
Vol 181 (1) ◽  
pp. 79-91 ◽  
Author(s):  
P J Lehner ◽  
E C Wang ◽  
P A Moss ◽  
S Williams ◽  
K Platt ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Influenza A ◽  
Cytotoxic T Lymphocyte ◽  
Gene Segment ◽  
Cell Subpopulation ◽  
Specific Lysis ◽  
Ctl Response ◽  
The Matrix ◽  
Limiting Dilution

The major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response is important in the clearance of viral infections in humans. After influenza A infection, a peptide from the matrix protein, M58-66, is presented in the context of the MHC allele HLA-A0201 and the resulting CTL response is detectable in most HLA-A0201 subjects. An initial study suggested that M58-66-specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene segments. We have addressed the significance of this observation by determining the expression of V beta 17 during the development of M58-66-specific CTL lines in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17 expansion correlated with M58-66-specific lysis. Limiting dilution analysis from five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000 and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)-specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response was dependent on previous viral exposure and specific V beta 17 expansion, as it was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from 13 subjects revealed extensive conservation in the CDR3 region including conservation of an arginine-serine motif. To test the dependence of this CTL response on the V beta 17 gene segment, peripheral blood lymphocytes were depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific CTL. In most cases such depletion blocked or severely reduced the generation of the M58-66-specific response, and under limiting dilution conditions could abolish M58-66-specific CTL precursors. These studies reveal the dependence of this natural human immune response on a particular TCR gene segment.

scholarly journals Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro.

1992 ◽  
Vol 175 (2) ◽  
pp. 609-612 ◽  
Author(s):  
S Nair ◽  
F Zhou ◽  
R Reddy ◽  
L Huang ◽  
B T Rouse
Keyword(s):  
Dendritic Cells ◽  
T Lymphocyte ◽  
Antigen Processing ◽  
Vaccine Development ◽  
Cytotoxic T Lymphocyte ◽  
Present Report ◽  
Soluble Proteins ◽  
Ph Sensitive ◽  
Ctl Response

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.

scholarly journals Fusogenic Liposome can be Used as an Effective Vaccine Carrier for Peptide Vaccination to Induce Cytotoxic T Lymphocyte (CTL) Response

2005 ◽  
Vol 28 (1) ◽  
pp. 192-193 ◽  
Author(s):  
Toshiki Sugita ◽  
Tomoaki Yoshikawa ◽  
Jian-Qing Gao ◽  
Mariko Shimokawa ◽  
Atushi Oda ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Effective Vaccine ◽  
Peptide Vaccination ◽  
Ctl Response ◽  
Vaccine Carrier
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