Brief Report: Dipyridamole Decreases Gut Mucosal Regulatory T-Cell Frequencies Among People With HIV on Antiretroviral Therapy
| Autor: | Kyle Holleran, Rhonda M. Brand, Kaleab Z. Abebe, Diane M. Comer, Ian McGowan, Delbert G. Gillespie, John W. Mellors, Bernard J.C. Macatangay, Joshua C. Cyktor, Cynthia Klamar-Blain, Ashley Zyhowski, Sharon A. Riddler, Edwin K. Jackson, Christina Mallarino-Haeger |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Adenosine Regulatory T cell Anti-HIV Agents Biopsy HIV Infections 030312 virology CD8-Positive T-Lymphocytes Placebo Lymphocyte Activation Gastroenterology T-Lymphocytes Regulatory Article 03 medical and health sciences Immune system Internal medicine medicine Extracellular Cytotoxic T cell Humans Pharmacology (medical) Intestinal Mucosa 0303 health sciences Cross-Over Studies business.industry Dipyridamole Middle Aged Flow Cytometry Infectious Diseases medicine.anatomical_structure Female business CD8 medicine.drug |
| Zdroj: | J Acquir Immune Defic Syndr |
| ISSN: | 1944-7884 |
| Popis: | Background We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine levels. Methods In this substudy, rectosigmoid biopsies were obtained from 18 participants (9 per arm), to determine whether 12 weeks of dipyridamole affects mucosal immune cells. Participants randomized to placebo were then switched to dipyridamole for 12 weeks while the treatment arm continued dipyridamole for another 12 weeks. We evaluated T-cell frequencies and plasma markers of microbial translocation and intestinal epithelial integrity. Linear regression models on log-transformed outcomes were used for the primary 12-week analysis. Results Participants receiving dipyridamole had a median 70.2% decrease from baseline in regulatory T cells (P = 0.007) and an 11.3% increase in CD8 T cells (P = 0.05). There was a nonsignificant 10.80% decrease in plasma intestinal fatty acid binding protein levels in the dipyridamole arm compared with a 9.51% increase in the placebo arm. There were no significant differences in plasma levels of β-D-glucan. In pooled analyses, there continued to be a significant decrease in regulatory T cells (-44%; P = 0.004). There was also a trend for decreased CD4 and CD8 T-cell activation. Conclusion Increasing extracellular adenosine levels using dipyridamole in virally suppressed HIV (+) individuals on antiretroviral therapy can affect regulation of gut mucosal immunity. |
| Databáze: | OpenAIRE |
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