title: Re-evaluation of PD-1 expression by T cells as a marker for immune exhaustion during SIV infection.
abstract: PD-1 expression is generally associated with exhaustion of T cells during chronic viral infections based on the finding that PD-1 expressing cells respond poorly to antigen activation and blockade of PD-1/PD-ligand interaction restores such antigen specific responses in vitro. We tested this hypothesis by examining PD-1 expression on virus-specific CD8 T cells and total T cells in vivo to determine whether PD-1 expression constitutes a reliable marker of immune exhaustion during SIV infection. The expression of PD-1 and Ki67 was monitored longitudinally on T cell subsets in peripheral blood, bone marrow, lymph node and rectal biopsy specimens from rhesus macaques prior to and post infection with pathogenic SIVmac239. During the course of infection, a progressive negative correlation was noted between PD-1 density and Ki67 expression in p11CM(+) CD8(+) T cells, as seen in other studies. However, for total and memory CD4 and CD8 T cells, a positive correlation was observed between PD-1 and Ki67 expression. Thus, while the levels of non-proliferating PD-1(+) p11CM(+) CD8 T cells were markedly elevated with progressing infection, such an increase was not seen on total T cells. In addition, total memory PD1(+) T cells exhibited higher levels of CCR5 than PD-1(-) T cells. Interestingly, few PD-1(+) CD8(+) T cells expressed CCR7 compared to PD-1(+) CD4 T cells and PD-1(-) T cells. In conclusion, overall PD1(+) T cells likely represent a particular differentiation stage or trafficking ability rather than exhaustion and in the context of chronic SIV infection, the level of PD-1 expression by T cells does not by itself serve as a reliable marker for immune exhaustion.
authors.affiliation: Division of Pathology, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Amancha
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rogers
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008253:Macaca mulatta; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*
chemical_list: D019394:Ki-67 Antigen; D061026:Programmed Cell Death 1 Receptor
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