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


Lilian Kolte, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 2650 Hvidovre, Denmark.


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+CD127low), 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.