T-regulatory cells infected with feline immunodeficiency virus up-regulate programmed death-1 (PD-1)

CD4(+)CD25(+) regulatory T (Treg) cells play a crucial role in the regulation of peripheral tolerance and immune response. Treg cells influence the nature and magnitude of immune responses, in particular to chronic infections with viruses such as HIV in humans and feline immunodeficiency virus (FIV) in cats. The co-stimulatory molecule programmed (cell) death-1 (PD-1) is expressed on T cells and antigen presenting cells. Interaction with its ligand, PD-L1, reduces CD4(+) and CD8(+) T-cell function, and may lead to dysfunction or exhaustion of T cells. In this study, lymphocytes from blood or lymph nodes of healthy cats were mock or FIV infected, and sorted into CD4(-), CD4(+)CD25(+) and CD4(+)CD25(-) subsets. Expression of FoxP3, PD-1 and PD-L1 mRNA relative to the housekeeping genes beta actin and tyrosine 3-monooxygenase was determined by quantitative reverse transcriptase PCR assays. Results indicated that CD4(+)CD25(+) cells had higher transcript numbers of FoxP3, PD-1 and PD-L1 than CD4(-) and CD4(+)CD25(-) cells (P<0.05). Acute in vitro FIV infection increased expression of FoxP3, PD-1 and PD-L1 in CD4(+)CD25(+) and CD4(+)CD25(-) cells, with highest relative expression in CD4(+)CD25(+) cells. These findings suggest that up-regulation of PD molecules in acutely FIV-infected lymphocytes may contribute to the immunosuppressive function of Treg cells in lentiviral infection.