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Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion

2013; Oxford University Press; Volume: 94; Issue: 4 Linguagem: Inglês

10.1189/jlb.0113018

1938-3673

Ilona Tóth, Anh Q. Le, Philip Hartjen, Adriana Thomssen, V Matzat, Clara Lehmann, Christoph Scheurich, Claudia Beisel, Philipp Busch, Olaf Degen, Ansgar W. Lohse, Thomas Eiermann, Gerd Fätkenheuer, Dirk Meyer‐Olson, Maximilian Bockhorn, Joachim Hauber, Jan van Lunzen, Julian Schulze zur Wiesch,

Immune Cell Function and Interaction

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 (∼10%) of peripheral Tregs. In contrast, we see high expression of CD73 on peripheral CD8(+) T cells. In HIV infection, CD73 is markedly reduced on all Teffs and Tregs, regardless of the memory subtype. On CD8(+) T cells, a positive correlation between CD73 expression and CD4 counts (P=0.0003) was detected. CD73 expression on CD8(+) T cells negatively correlated with HLA-DR (<0.0001) and PD1 (P=0.0457) expression. The lower CD73 expression on CD8(+) T cells was partially reversible after initiation of ART (P=0.0016). Functionally, we observed that CD8(+)CD73(+) T cells produce more IL-2 upon HIV-specific and unspecific stimulation than their CD73(-) counterparts and show a higher proliferative capacity. These data indicate that down-regulation of CD73 on CD8(+) T cells correlates with immune activation and leads to functional deficits in HIV infection.