Developmental regulation of P-glycoprotein activity within thymocytes results in increased anti-HIV protease inhibitor activity
| Autor: | Matthew Morrow, John W. Sleasman, Sarah K. Ho, Maureen M. Goodenow, Soichi Haraguchi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male ATP Binding Cassette Transporter Subfamily B Immunology HIV Infections Thymus Gland CD8-Positive T-Lymphocytes Virus Replication Pi Humans Immunology and Allergy Cytotoxic T cell HIV Protease Inhibitor ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger P-glycoprotein Messenger RNA biology Infant Newborn Infant HIV Protease Inhibitors Cell Biology Virology Molecular biology Thymocyte Viral replication HIV-1 biology.protein Female CD8 |
| Zdroj: | Journal of Leukocyte Biology. 90:653-660 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0111-009 |
| Popis: | The thymus harbors HIV-1 and supports its replication. Treatment with PI-containing ART restores thymic output of naïve T cells. This study demonstrates that CXCR4-using WT viruses are more sensitive to PI in fetal thymcocytes than mature T cells with average IC50 values for two PIs, RTV and IDV, of 1.5 nM (RTV) and 4.4 nM (IDV) in thymocytes versus 309.4 nM (RTV) and 27.3 nM (IDV) in mature T cells. P-gp activity, as measured using Rh123 efflux and quantitation of P-gp mRNA, increased with thymocyte maturation into CD4 and CD8 lineage T cells. P-gp activity is developmentally regulated in the thymus. Thymocytes developed increased levels of P-gp activity as maturation from DP to SP CD4 or CD8 T cells occurred, although CD4 T cells acquired activity more rapidly. Reduced P-gp activity in thymocytes is one mechanism for effectiveness of PI therapy in suppressing viral replication in the thymus and in reconstitution of naïve T cells, particularly among children receiving PI-containing ART. |
| Databáze: | OpenAIRE |
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