Progressive Expansion of an L-Selectin—Negative CD8 Cell with Anti—Feline Immunodeficiency Virus (FIV) Suppressor Function in the Circulation of FIV-Infected Cats
ABSTRACT The acute stage of feline immunodeficiency virus (FIV) infection is characterized by the appearance of a major CD8 subpopulation with reduced expression of the CD8 beta chain (CD8alpha+betalo). CD8 antiviral activity was subsequently shown to be mediated by the CD8alpha+betalo phenotype, which is the dominant CD8 phenotype in long-term infected cats. Two- and three-color flow cytometric analysis demonstrated that the CD8alpha+betalo subset is L-selectin negative (CD62L-) and has increased expression of CD44, CD49d, and CD18, consistent with an activation phenotype. The CD8alpha+betaloCD62L- cells but not the CD8alpha+betahiCD62L+ cells demonstrated strong antiviral activity in the FIV acute-infection assay. The progressive expansion of the CD8alpha+betaloCD62L- effector subset cells in FIV-infected cats parallels that seen in human immunodeficiency virus (HIV)-infected patients, suggesting that failure in homeostatic mechanisms regulating lymphocyte activation or trafficking (or both) may be a consequence of both HIV and FIV infections.
- SourceAvailable from: Filippo Castiglione
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- "CD8β chain and the complete disappearance of the L-selectin CD62L surface molecule . These CD8β low CD62L − T cells, hereafter referred to as CD8β low cells, persist throughout the course of infection. "
ABSTRACT: Studies of the response of the immune system to feline immunodeficiency virus (FIV) during primary infection have shown that a subpopulation of CD8(+) T-cells with an activated phenotype and reduced expression of the CD8β chain (denoted CD8β(low) T cells) expands to reach up to 80% of the total CD8(+) T cell count. The expansion of this subpopulation is considered to be a signature of FIV and an indicator of immune system alteration. We use a simple mathematical formalism to study the relationships over time between the dose of infection, the size of the CD8β(low) population, and the circulating viral load in cats infected with FIV. Viremia profiles are described using a combination of two exponential laws, whereas the CD8β(low) percentage (out of the total CD8(+) population) is represented by a Gompertz law including an expansion phase and a saturation phase. Model parameters are estimated with a population approach using data from 102 experimentally infected cats. We examine the dose of infection as a potential covariate of parameters. We find that the rates of increase of viral load and of CD8β(low) percentage are both correlated with the dose of infection. Cats that develop strong acute viremia also show the largest degree of CD8β(low) expansion. The two simple models are robust tools for analysing the time course of CD8β(low) percentage and circulating viral load in FIV-infected cats and may be useful for generating new insights on the disease and on the design of therapeutic strategies, potentially applicable to HIV infection.Computational and Mathematical Methods in Medicine 09/2012; 2012:342602. DOI:10.1155/2012/342602 · 0.77 Impact Factor
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- "L-selectin (CD62L) was examined as a marker primarily found on naïve lymphocytes as well as some central memory T cells [36-39]. Loss of L-selectin expression has previously been shown to correlate with FIV antiviral activity . Following repeated mucosal exposure to heterologous cells, the percentage of CD4+ T cells expressing L-selectin were increased in the gut tissue, IEL (p = 0.028) and decreased in iliac lymph node (p = 0.0031) (Fig 1a). "
ABSTRACT: Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV) model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control) and then cats were vaginally challenged with cell-associated or cell-free FIV. Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN) expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus) can be modulated by mucosal exposure to uninfected heterologous cells.Retrovirology 05/2010; 7:49. DOI:10.1186/1742-4690-7-49 · 4.19 Impact Factor
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- "Experimental infection with FIV results in early, acute infection characterised by pyrexia, dullness, leucopenia and is associated with an inversion of the CD4+/CD8+ T cell ratio, followed by a progressive decline in circulating CD4+ T cells (Ackley et al., 1990; Tompkins et al., 1991; Callanan et al., 1992) and a sustained increase in CD8+ T cells (Willett et al., 1993; Bucci et al., 1998; Gebhard et al., 1999). A prolonged subclinical phase then occurs (Diehl et al., 1995) and in many specific-pathogen free environments, this phase of infection continues beyond the time-span of many studies, although one long-term experiment reported 6/24 cats progressing to the AIDS stage of disease between 3.8 and 5.8 years post-infection (Mathiason-DuBard et al., 1998). "
ABSTRACT: Feline immunodeficiency virus (FIV), like human immunodeficiency virus (HIV)-1, is a neurotropic lentivirus, and both natural and experimental infections are associated with neuropathology. FIV enters the brain early following experimental infection, most likely via the blood-brain and blood-cerebrospinal fluid barriers. The exact mechanism of entry, and the factors that influence this entry, are not fully understood. As FIV is a recognised model of HIV-1 infection, understanding such mechanisms is important, particularly as HIV enters the brain early in infection. Furthermore, the development of strategies to combat this central nervous system (CNS) infection requires an understanding of the interactions between the virus and the CNS. In this review the results of both in vitro and in vivo FIV studies are assessed in an attempt to elucidate the mechanisms of viral entry into the brain.The Veterinary Journal 04/2010; 188(3):260-9. DOI:10.1016/j.tvjl.2010.03.022 · 1.76 Impact Factor