Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1–infected patients on treatment

K Grabmeier-Pfistershammer… - JAIDS Journal of …, 2011 - journals.lww.com
K Grabmeier-Pfistershammer, P Steinberger, A Rieger, J Leitner, N Kohrgruber
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2011journals.lww.com
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 …
Abstract
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.
Lippincott Williams & Wilkins