Expression levels of P-glycoprotein in peripheral blood CD8+ T lymphocytes from HIV-1-infected patients on antiretroviral therapy

Abstract

In this study, we aimed to measure P-glycoprotein (P-gp) expression in CD8(+) T lymphocytes of HIV-1-infected patients, to investigate how P-gp levels are affected by antiretroviral therapy (ART) in HIV-1 infection, and to assess the value of using P-gp expression to predict virologic response to ART. Peripheral blood mononuclear cells (PBMCs) were obtained from a cohort of HIV-1‑infected patients in China: 140 patients on ART, and 49 ART-naïve patients. We also enrolled 24 healthy blood donors as the controls. The expression levels of P-gp in CD8(+) T cells of HIV-1-infected patients were evaluated by quantitative reverse transcription PCR, ELISA and flow cytometry. A high inter-individual variability was observed in the CD8(+) T cells of both HIV-1-infected patients and healthy donors; however, the expression levels of P-gp were significantly higher in the HIV-1-infected group on ART compared to the ART-naïve group. The relative proportion of P-gp(+)CD8(+) T cells inversely correlated with the blood CD4(+) T cell count in the HIV-1‑infected patients on ART (r=-0.3343, P=0.0375). Groups of both good and poor responders showed significantly elevated levels of P-gp(+)CD8(+) T cells. The percentage of P-gp(+)CD8(+) T cells appeared to provide a sensitive estimate of the virologic response to ART compared to the CD4(+) T cell count. Our results suggest that P-gp expression varies among HIV-1‑infected patients, but is significantly higher in HIV-1‑infected patients on ART. The overexpression of P-gp is involved in ART initiation during HIV-1 infection, and P-gp(+)CD8(+) T cells may be an additional criterion for the evaluation of the antiretroviral response to ART.

MDR1 in immunity: friend or foe?

“…89 In contrast, the increased MDR1 expression at transcriptomic and protein levels detected on CD8 + T cells in treated patients is associated with a better efflux capacity. 90 …”

“…The hostile tumor micro-environment and its chemical composition must indeed shape the immune infiltrate, and MDR1 expression by anti-tumor immune cells may favor their preservation despite harsh environmental conditions. The immune infiltrate is also modulated by MDR1-associated anti-neoplastic agents, 90,101 and evaluation of MDR1 level on immune cells could be an indicator of these treatments’ effects.…”

Antiretroviral Therapy through Barriers: A Prominent Role for Nanotechnology in HIV-1 Eradication from Sanctuaries

“…Indeed, various pharmacological formulations of ARVs have been tested vaginally or orally for a pre-exposure prophylaxis of HIV-1 in women, but the presence of P-gp significantly diminishes the efficacy of the administered ARV [43]. Finally, P-gp can be highly overexpressed in response to therapy administration, as well documented by studies on CD8+ T lymphocytes isolated from the peripheral blood of HIV-1-infected patients under ARV treatment [44]. In conclusion, P-gp system plays a crucial role in preventing the penetration of ARVs into HS, and overcoming this barrier is of primary importance for proper viral eradication.…”

Perplexing Role of P-Glycoprotein in Tumor Microenvironment

“…Currently, several new drug discovery projects have an array of novel pro-drug compounds in pipeline to bypass or exert a more sustained P-gp inhibition (11). Interestingly, over the past two and half decade accumulating evidence suggested that the expression of P-gp in inflammatory immune cell subset (12)(13)(14)(15). This could exert a potential anti-cancer cytotoxic functionality.…”