title: CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of feline immunodeficiency virus infection.
abstract: Acute lentiviral infection is characterized by early CD8(+) cytotoxic T cell (CTL) activity and a subsequent decline in plasma viremia. However, CD8(+) lymphocytes fail to eliminate the virus and a progressive T cell immune dysfunction develops during the course of chronic lentiviral infection. To further define this CD8(+) immune dysfunction we utilized PARR (PCR for antigen receptor rearrangements), a technique which measures clonally expanded lymphocyte populations by comparison of highly conserved T cell receptor (TCR) regions to identify the prevalence of clonal CD8(+) T cells following FIV infection. We then compared phenotype, mRNA profiles, CD8(+) proliferation and plasma viremia during acute and chronic infection for PARR positive (PARR(+)) and PARR negative (PARR(-)) Feline Immunodeficiency Virus (FIV) infected cats. We demonstrated that approximately forty percent of the FIV(+) cats examined exhibit CD8(+) clonality compared to none of the FIV(-) control cats. There were no phenotypic differences between PARR(+) and PARR(-) CD8(+) lymphocytes from FIV(+) cats but retrospective analysis of plasma viremia over the course of infection revealed a delayed peak in plasma viremia and a decline in lymphocyte counts were observed in the PARR(+) group during acute infection. CD8(+) lymphocytes isolated from chronically infected PARR(-) cats exhibited significantly higher mRNA expression of IFN-γ and IL-2 following mitogenic stimulation when compared to PARR(+) CD8(+) lymphocytes. These data suggest that clonal CD8(+) expansion may be related to impaired control of acute viremia and less effective CD8(+) anti-viral function. Using PARR to assess changes in CD8(+) clonality during the progression from acute to chronic FIV infection may help to better characterize the factors which contribute to CD8(+) anergy and lentiviral persistence.
authors: Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607, United States.
authors: Michelle M
authors: MM
authors: Miller
authors: Elizabeth M
authors: EM
authors: Thompson
authors: Steven E
authors: SE
authors: Suter
authors: Jonathan E
authors: JE
authors: Fogle
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002371:Cat Diseases / Q000235:genetics / Q000276:immunology*; D002415:Cats; D060966:Clonal Selection, Antigen-Mediated / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D015329:Gene Rearrangement, T-Lymphocyte; D016089:Immunodeficiency Virus, Feline; D016180:Lentivirus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014766:Viremia / Q000235:genetics / Q000276:immunology / Q000662:veterinary
chemical_list: D016827:CD8 Antigens; D016207:Cytokines; D012333:RNA, Messenger