title: 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.
abstract: This study determines levels of regulatory T cells (T(regs)), naive T(regs), 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 T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (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 (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) 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 T(regs) were elevated significantly in HIV-infected patients (P<0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P=0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark. lilian@kolte.dk
authors.forename: L
authors.initials: L
authors.lastname: Kolte
authors.forename: J C
authors.initials: JC
authors.lastname: Gaardbo
authors.forename: K
authors.initials: K
authors.lastname: Skogstrand
authors.forename: L P
authors.initials: LP
authors.lastname: Ryder
authors.forename: A K
authors.initials: AK
authors.lastname: Ersbøll
authors.forename: S D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016014:Linear Models; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger