No abstract

Recent studies indicate that murine Tregs highly express the ENTDP1, as well as the 5=-NT and thereby, suppress Teff function by extracellular adenosine production. Furthermore, CD73 seems to play a role as costimulatory molecule for T cell differentiation. In this study, we analyzed the expression of CD73 on peripheral and lymph nodal Teffs and Tregs in a cohort of 95 HIV patients at different stages of disease, including LTNP and ECs. In contrast to murine Tregs, CD73 was only expressed on a small minority (ϳ10%) of peripheral Tregs. In contrast, we see high expression of CD73 on peripheral CD8ϩ T cells. In HIV infection, CD73 is markedly reduced on all Teffs and Tregs, regardless of the memory subtype. On CD8 ϩ T cells, a positive correlation between CD73 expression and CD4 counts (Pϭ0.0003) was detected. CD73 expression on CD8 ϩ T cells negatively correlated with HLA-DR (Ͻ0.0001) and PD1 (Pϭ0.0457) expression. The lower CD73 expression on CD8 ϩ T cells was partially reversible after initiation of ART (Pϭ0.0016). Functionally, we observed that CD8 ϩ CD73 ϩ T cells produce more IL-2 upon HIV-specific and unspecific stimulation than their CD73 Ϫ counterparts and show a higher proliferative capacity. These data indicate that down-regulation of CD73 on CD8ϩ T cells correlates with immune activation and leads to functional deficits in HIV infection.