Mucosal Immunopathogenesis of Feline Immunodeficiency Virus (FIV)
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Date
2006-05-02
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Abstract
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have profound effects on the structure, function and leukocyte populations of the gastrointestinal tract. Intestinal tract changes have been identified in SIV-infected macaques as early as 1-2 weeks following experimental infection, and in HIV-infected humans within months of infection. FIV is an established model of HIV immune dysfunction but the mucosal pathogenesis of FIV infection has not been well studied. In the present study, we (1) identify the normal phenotype of feline small intestinal leukocyte populations; (2) characterize changes occurring in the gastrointestinal immune system of acutely and chronically FIV-infected cats, and (3) address the impact that different inoculum types (cell-associated versus cell-free virus) may have in early immune alterations.
The methodology for isolation of intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) was optimized to provide samples of high yield and purity for use in phenotypic and functional assays. We found the phenotype IEL, LPL and Peyer's patches of cats to be similar to that reported in other species, except for the expression of CD5 and MHC II. Profound loss of IEL and mesenteric lymph node cells was observed in persistent FIV infection. In addition, we detected significant immune dysregulation of the medial iliac lymph node that may involve aberrant homing of CD4+ T-cells. Loss of IEL was associated with the induction of apoptosis that occurred in a significant proportion of IEL one day after inoculation with cell-associated but not cell-free FIV. In addition to differential induction of apoptosis, we also identified significant differences in phenotype of leukocyte populations sampled very early after inoculation with cell-associated versus cell-free FIV in every tissue examined.
Thus, immune dysfunction clearly occurs in the mucosal immune system of cats infected with FIV. Furthermore, these findings expand the current knowledge of lentiviral pathogenesis by demonstrating that changes occur much earlier than has been previously reported, and that inoculum type profoundly influences the early immune dysregulation observed.
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Pathogenesis, LPL, IEL, HIV, FIV, Mucosal
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Degree
PhD
Discipline
Immunology
