Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1-infected patients on treatment.
PD-1 expression on T cells correlates with T-cell exhaustion and disease progression in HIV-infected patients. Previous studies have shown that combinational antiretroviral therapy induced viral suppression results in immune restoration and reduced PD-1 expression. However, a significant number of patients fail to restore CD4 T cells despite suppression of HIV replication below limit of quantification. In this study, we have analyzed PD-1 expression on CD4 and CD8 T cells in patients with poor immune reconstitution despite successful highly active antiretroviral therapy. We found that T cells of such patients express significantly higher levels of PD-1 than patients who had normal recovery of CD4 cells after treatment. In contrast, failing immune reconstitution was not associated with the expression of activation markers, indicating that PD-1 is a unique marker for failing immune reconstitution despite viral suppression. Furthermore, we show that T cells from patients with poor immune recovery differ from T cells of elderly in respect of their marker profile. PD-1 expression negatively correlated with individual CD4 cell counts, and PD-1 expressing T cells were more prone to programmed death ligand-mediated inhibition of T-cell proliferation, indicating that PD-1-mediated T-cell suppression may have a role in impaired immune reconstitution in HIV patients.
Grabmeier-Pfistershammer
Katharina
K
Department of Dermatology, Division of Immunology, Center of Physiology, Pathophysiology and Immunology, Medical University Vienna, Vienna, Austria. katharina.pfistershammer@meduniwien.ac.at
Steinberger
Peter
P
Rieger
Armin
A
Leitner
Judith
J
Kohrgruber
Norbert
N
D000328:Adult; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage; D015703:Antigens, CD / Q000032:analysis*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor
D019380:Anti-HIV Agents; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor