Re-evaluation of PD-1 expression by T cells as a marker for immune exhaustion during SIV infection

• Published in: PloS one Vol. 8; no. 3; p. e60186
• Main Authors: Hong, Jung Joo, Amancha, Praveen K, Rogers, Kenneth, Ansari, Aftab A, Villinger, Francois
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; Biology; Biopsy; Bone marrow; CC chemokine receptors; CCR5 protein; CCR7 protein; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Chronic infection; Correlation; Exhaustion; HIV; Human immunodeficiency virus; Immunological memory; In vivo methods and tests; Infections; Ki-67 Antigen - metabolism; Kinases; Lymph nodes; Lymphocytes; Lymphocytes T; Macaca mulatta; Medicine; Memory cells; Monkeys & apes; PD-1 protein; Peripheral blood; Programmed Cell Death 1 Receptor - metabolism; Rectum; Simian Acquired Immunodeficiency Syndrome - metabolism; Simian Immunodeficiency Virus - pathogenicity; Veterinary Science; Viral infections; Viruses; England; Atlanta Georgia; Georgia; United Kingdom > UK; United States > US; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060186

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.