Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

摘要

This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3⁺CD4⁺CD25⁺CD127^low), naive Tregs (CD3⁺CD4⁺CD25⁺CD45RA⁺) and activation markers (CD38⁺human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4⁺ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P < 0·001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV-infected patients (P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4⁺ cells (P = 0·038). In summary, Treg levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV-infection.