CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of Feline Immunodeficiency Virus infection

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.