Background:  PD- 1 expression on T cells correlates with T cell exhaustion and disease progression in HIV infected patients. HAART results in reduced PD-1 expression and immune restoration in most patients. However, a minority of patients fail to reconstitute their CD4⁺ T cells, in spite of successful suppression of HIV replication. In this study, we assessed PD-1 expression on T lymphocytes in patients with failing immune recovery.

Methods:  PD-1 expression was analyzed by flow cytometry of T cells gained from HIV-1-infected patients showing a defect in immune reconstitution as defined by less than 200 CD4 cells in spite of viral suppression of at least 1 year and compared to PD-1 levels on T cells of HAART-naïve patients and patients with immune recovery. Statistical significance was determined by students t-test.

Results:  We found low amounts of PD-1 expression on CD4 or CD8 T cells in healthy controls (n = 10) and patients on HAART with sustained virological suppression and immune recovery to >500 CD4 T cells (n = 10). In contrast, patients without recovery of CD4 T cells (n = 10) exhibited significantly higher amounts of PD-1 expression on CD4 T cells (p = 0.008), but not on CD8 T cells. In addition, no significant difference in PD-1 expression on CD4 T cells was observed in patients with failing immune reconstitution as compared to patients without antiretroviral treatment. Among CD4 T cells, PD-1 was detected on both central (CCR7⁺CD45RA^–), as well as effector memory (CCR5⁺CD45RA^–) subsets but not on naïve cells. In addition to PD-1, its ligand PD-L1 was expressed at significantly higher levels on CD4 T cells of patients with poor as compared to patients with good immune recovery (p = 0.004). In contrast, no significant relation with CD4 cell numbers could be observed when analyzing the expression CD27, CD28, PD-L2, and CTLA-4 on T cells.

Conclusions:  We therefore conclude that persistent increase in PD-1/PD-L1 expression on T cells, in spite of successful ART, defines patients with poor immune reconstitution. Ongoing immune activation and inhibition of T cell proliferation via PD-1/PD-L1 might contribute to the insufficient recovery of T cell function and number.