Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

Hayes, Kathleen; Köksoy, Sadi; Phipps, Andrew J.; Buck, Wayne R.; Kociba, Gary J.; Mathes, Lawrence E.

doi:10.1128/jvi.79.13.8237-8242.2005

Cited by 4 publications

(3 citation statements)

References 26 publications

(21 reference statements)

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“…The method proved valuable in either situation. During the early stages of infection, characterized by acute viral replication and vigorous cell-mediated immune responses [ 18 , 23 ], the assay detected levels of Env-specific CTL activity in the PBMCs of infected cats similar to those previously reported with 51 Cr CTL assays using SV40-immortalized or primary feline fibroblasts infected by recombinant vaccinia viruses [ 18 , 24 ], with no need for the effector cells to be restimulated ex vivo , a procedure frequently necessary when using the standard Cr 51 assay [ 25 ]. In contrast, in the chronically infected cells we detected no measurable Env-specific CTL activity even when the effector PBMCs were restimulated ex vivo .…”

Section: Discussionsupporting

confidence: 69%

A novel method for producing target cells and assessing cytotoxic T lymphocyte activity in outbred hosts

et al. 2009

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Background: Cytotoxic T lymphocytes play a crucial role in the immunological control of microbial infections and in the design of vaccines and immunotherapies. Measurement of cytotoxic T lymphocyte activity requires that the test antigen is presented by target cells having the same or compatible class I major hystocompatibility complex antigens as the effector cells. Conventional assays use target cells labeled with 51 chromium and infer cytotoxic T lymphocyte activity by measuring the isotope released by the target cells lysed following incubation with antigen-specific cytotoxic T lymphocytes. This assay is sensitive but needs manipulation and disposal of hazardous radioactive reagents and provides a bulk estimate of the reporter released, which may be influenced by spontaneous release of the label and other poorly controllable variables. Here we describe a novel method for producing target in outbred hosts and assessing cytotoxic T lymphocyte activity by flow cytometry.

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Section: Discussionsupporting

confidence: 69%

A novel method for producing target cells and assessing cytotoxic T lymphocyte activity in outbred hosts

et al. 2009

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“…In a chronic LCMV infection model, continuous thymic output does not appear to be required to maintain CD8 T cell responses, although a T cell defi cit was observed at day 30 after infection (26). In contrast, thymectomy is associated with loss of CTL activity in cats persistently infected by a feline lentivirus (27). Our data are consistent with reports describing antigen dependence for chronic pathogen-specifi c T cell maintenance, especially as newly primed cells may be important for preserving the population of virus-specifi c T cells ( Fig.…”

Section: Brief Definitive Reportmentioning

confidence: 98%

Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection

Vezys¹,

Masopust

Kemball³

et al. 2006

The Journal of Experimental Medicine

171

188

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Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific T cells in chronically infected hosts are often phenotypically and functionally variable, as well as distinct from T cells responding to nonpersistent infections; this phenotypic heterogeneity has been attributed to an ongoing reencounter with antigen. Paradoxically, maintenance of memory CD8 T cells to acutely resolved infections is antigen independent, whereas there is a dependence on antigen for T cell survival in chronically infected hosts. Using two chronic viral infections, we demonstrate that new naive antigen-specific CD8 T cells are primed after the acute phase of infection. These newly recruited T cells are phenotypically distinct from those primed earlier. Long-lived antiviral CD8 T cells are defective in self-renewal, and lack of thymic output results in the decline of virus-specific CD8 T cells, indicating that newly generated T cells preserve antiviral CD8 T cell populations during chronic infection. These findings reveal a novel role for antigen in maintaining virus-specific CD8 T cells during persistent infection and provide insight toward understanding T cell differentiation in chronic infection.

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“…Likewise, percentages of naïve CD8 + lymphocytes were also reduced with FIV infection, resulting in a predominance of CD8 + CD45RA neg (memory CD8 + ) cells, as reported for FIV-infected adult cats (91). Depletion of naïve cells may have occurred through lytic infection, activation-induced apoptosis, activation of immunosuppressive regulatory T cells, transition from a naïve to a memory phenotype, or thymus insufficiency (14,(92)(93)(94)(95)(96).…”

Section: Thymus Pathogenesismentioning

confidence: 52%

Immunopathogenesis of feline immunodeficiency virus infection in the fetal and neonatal cat

Holly¹

2007

Front Biosci

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The global incidence of pediatric HIV infection is estimated at 2.3 million children, most acquiring the infection from their mothers in utero, peripartum, or postpartum. Pediatric HIV infection typically causes a rapidly progressive disease when compared with adult infection, due in part to the profound susceptibility of the neonatal thymus to productive infection or degenerative changes. Failed production of naive T-lymphocytes further limits the success of antiviral therapy to restore immunologic function. In this review, we explore the use of feline immunodeficiency virus (FIV) infection of domestic cats as an animal model for pediatric HIV infection. Cats infected with FIV represent the smallest host of a naturally occurring lentivirus, and the immunodeficiency syndrome elicited by FIV infection is similar to that of HIV-AIDS. The feline-FIV model uniquely reproduces several key aspects of immunosuppressive lentivirus infection of the thymus, allowing investigators to define viral determinants of pathogenicity, influence of host age on disease outcome, and therapeutic strategies to restore thymus function.

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Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

Cited by 4 publications

References 26 publications

A novel method for producing target cells and assessing cytotoxic T lymphocyte activity in outbred hosts

A novel method for producing target cells and assessing cytotoxic T lymphocyte activity in outbred hosts

Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection

Immunopathogenesis of feline immunodeficiency virus infection in the fetal and neonatal cat

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